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1 
Fisiologia Animal 
Fisiologia	
  Animal	
  
•  Apresentação do programa da disciplina e 
respectiva bibliografia 
•  Normas de avaliação da disciplina 
•  Capítulo 1: Controlo Nervoso 
Fisiologia Animal 
Docentes	
  
•  Paulo	
  F.	
  Santos	
  
–  Email:	
  pfsantos@ci.uc.pt	
  
–  Gabinete:	
  Fac.	
  Medicina,	
  2º	
  piso,	
  sala	
  302B	
  
–  Horário	
  de	
  atendimento:	
  Sexta-­‐feira,	
  11-­‐12h	
  
•  Emília	
  Duarte	
  
•  António	
  Moreno	
  
•  Rosa	
  Santos	
  
•  Luís	
  M.	
  Rosário	
  
2 
Fisiologia Animal 
Programa	
  
•  Controlo	
  Nervoso	
  
•  Músculos	
  e	
  Movimento	
  Animal	
  
•  O	
  Sistema	
  Cardiovascular	
  e	
  o	
  Transporte	
  
Interno	
  
•  Troca	
  de	
  Gases	
  e	
  Equilíbrio	
  Ácido-­‐base	
  
•  O	
  Rim	
  e	
  a	
  Regulação	
  dos	
  Líquidos	
  do	
  Corpo	
  
Fisiologia Animal 
Bibliografia	
  
•  Silverthorn,	
  D.U.	
  (2013)	
  Human	
  Physiology:	
  An	
  Integrated	
  
Approach	
  (6ª	
  Ed)	
  Pearson	
  Ed.	
  
•  Fox,	
  S.I.	
  (2011)	
  Human	
  Physiology	
  
	
  (12ª	
  Ed)	
  McGraw-­‐Hill	
  
	
  
•  Moyes,	
  C.D.	
  (2008)	
  Principles	
  of	
  animal	
  physiology	
  (2ª	
  Ed)	
  
Benjamim	
  Cunings	
  Ed	
  	
  
•  Silverthorn,	
  D.U.	
  (2010)	
  Fisiologia	
  Humana:	
  uma	
  abordagem	
  
integrada	
  (5ª	
  Ed)	
  Artmed	
  Ed	
  
•  Seeley	
  .	
  Stephens	
  .	
  Tate	
  (2005)	
  Anatomia	
  &	
  Fisiologia	
  (6ª	
  Ed)	
  
Lusodidacta	
  Ed	
  	
  
3 
Fisiologia Animal 
Fisiologia	
  Animal	
  
•  Avaliação	
  
–  Apresentação	
  oral 	
   	
   	
   	
  10%	
  
–  Avaliação	
  das	
  aulas	
  prágcas 	
   	
  15%	
  
• Empenho,	
  preparação	
  
• Avaliação	
  no	
  exame	
  P	
  
–  Exame 	
   	
   	
   	
   	
   	
  75%	
  
• 1ªP	
  +	
  2ªP	
  ou	
  Ex	
  Ep.	
  Normal	
  
• Ex.	
  Ep	
  Rec.	
  
Fisiologia Animal 
Importante	
  
•  Proibido	
  realizar	
  gravações	
  
áudio	
  ou	
  vídeo	
  durante	
  as	
  
aulas.	
  
•  Conhecer	
  o	
  “Regulamento	
  
Disciplinar	
  dos	
  Estudantes	
  da	
  
Universidade	
  de	
  Coimbra”	
  
–  Disponível	
  no	
  material	
  de	
  apoio.	
  
	
  
4 
Fisiologia Animal 
Controlo	
  nervoso	
  
Fisiologia Animal 
Sistema	
  nervoso	
  
Sensory imput 
Motor output 
Sensory Receptor 
Effector 
SNC SNP 
5 
Fisiologia Animal Silverthorn, Human physiology (2001) 2 ed. 
Fisiologia Animal 
Evolução	
  do	
  SN	
  nos	
  animais	
  
•  Esponjas	
  
–  Único	
  filo	
  que	
  não	
  possui	
  SN	
  
•  Cnidários	
  
–  SN	
  simples,	
  em	
  forma	
  de	
  rede	
  
–  Não	
  possuem	
  controlo	
  de	
  acções	
  complexas	
  
–  Pouca	
  coordenação	
  
•  Platelmites	
  
–  SN	
  já	
  apresenta	
  acgvidade	
  associagva	
  
–  Encéfalo	
  primigvo	
  e	
  cordões	
  nervosos	
  
•  Anelídeos	
  
–  Evolução	
  do	
  esquema	
  presente	
  nas	
  planárias	
  
–  CNS	
  ligado	
  a	
  outras	
  partes	
  do	
  organismo	
  por	
  nervos	
  
periféricos	
  
6 
Fisiologia Animal 
Evolução	
  do	
  sistema	
  nervoso	
  
Fisiologia Animal Camplbell, Bilogiy (1999) 5 ed. 
Sistema nervoso 
central (SNC) 
Sistema nervoso 
periférico (SNP) 
Encéfalo 
Medula espinal 
Nervos cranianos 
Gânglios 
Nervos espinais 
7 
Fisiologia Animal 
Organização	
  do	
  
sistema	
  nervoso	
  
Silverthorn, Human physiology (2001) 2 ed. 
Fisiologia Animal 
Organização	
  celular	
  do	
  SN	
  
•  Neurónios	
  
–  O	
  cérebro	
  humano	
  contém	
  cerca	
  de	
  100	
  biliões	
  de	
  
neurónios	
  (1011)	
  
–  Aproximadamente	
  o	
  número	
  de	
  estrelas	
  da	
  nossa	
  
galáxia	
  
•  Células	
  da	
  glia	
  
8 
Fisiologia Animal 
Neurónio	
  
PT-­‐Br	
   PT-­‐Pt	
  
Dendritos	
   Dendrites	
  
Axônio	
   Axónio	
  
Neurônio	
   Neurónio	
  
Consgpação	
   Obsgpação	
  
Fisiologia Animal 
Neurónios	
  
9 
Fisiologia Animal 
Comprimento	
  dos	
  neurónios	
  	
  
Fisiologia Animal 
Células	
  da	
  glia	
  
Silverthorn, Human physiology (2010) 5 ed. 
10 
Fisiologia Animal 
Células	
  da	
  glia	
  
Silverthorn, Human physiology (2010) 5 ed. 
Fisiologia Animal 
Homem	
  vs.	
  Computador	
  
11 
Fisiologia Animal 
Medição	
  dos	
  potenciais	
  de	
  membrana	
  
Voltímetro 
Microeléctrodo 
Campbell (1999) Biology (4ª Ed) 
Membrana!
plasmática 
Eléctrodo de!
referência 
Axónio 
Fisiologia Animal 
Axónio	
  gigante	
  da	
  lula	
  
12 
Fisiologia Animal 
Potencial	
  elétrico	
  
•  Como	
  é	
  que	
  as	
  nossas	
  células	
  geram	
  esse	
  
potencial	
  elétrico	
  de	
  membrana?	
  
Fisiologia Animal 
•  R	
  =	
  Constante	
  dos	
  gases	
  perfeitos	
  
•  1,987cal/ºK.mol	
  
•  T	
  =	
  Temperatura	
  (ºK	
  =	
  ºC+273)	
  
•  Z	
  =	
  Valência	
  do	
  ião	
  
•  F	
  =	
  Constante	
  de	
  Faraday	
  
•  23060	
  cal/V.mol	
  
Equação de Nernst 
Walther	
  Nernst	
  
13 
Fisiologia Animal 
? mV	
[K+] = 150	
[Na+] = 15	
[Cl-] = 10	
A-	
[K+] = 5	
[Na+] = 150	
[Cl-] = 120	
+	
+	
+	
 +	
+	
+	
+	
-	
-	
-	
-	
-	
-	
-	
 +	
Fisiologia Animal 
Potencial	
  de	
  repouso	
  
Vm =
1,987× (273+37)
23060
ln 100×5+3×150+0×10
100×150+3×15+0×120
Vm = 0,0267ln
950
15040
Vm = -0,0737V
Vm = -73mV
•  PK+>>PNa+>PCl-­‐	
  
•  PK+=	
  100	
  
•  PNa+=3	
  
•  PCl-­‐=0	
  
14 
Fisiologia Animal 
Células	
  excitáveis	
  
•  Neurónios	
  
•  Células	
  musculares	
  
•  Um	
  esgmulo	
  pode	
  induzir	
  alteração	
  no	
  
potencial	
  de	
  membrana	
  
–  Alteração	
  na	
  permeabilidade	
  das	
  membranas	
  
Fisiologia Animal 
Tempo (ms) 
Po
te
nc
ia
l d
e 
m
em
br
an
a 
(m
V)
 Diferença do potencial de membrana (Vm) 
Alterações	
  no	
  potencial	
  de	
  membrana	
  
Despolarização Repolarização Hiperpolarização 
Vm 
Diminui Vm 
aumenta 
Silverthorn, Human physiology (2001) 2 ed. 
15 
Fisiologia Animal 
Alterações	
  do	
  potencial	
  da	
  membrana	
  após	
  
esMmulação	
  da	
  célula 
Moffett et al. (1993) Human Physiology (2ª Ed) 
Potencial de 
acção 
Potenciais graduais 
Tempo 
Po
te
nc
ia
l d
e 
m
em
br
an
a 
 (m
V)
 
Estímulos 
-90 
-70 
0 
+60 (ENa) 
(EK) 
Potencial limiar 
Fisiologia Animal 
Como	
  é	
  que	
  os	
  esOmulos	
  
induzem	
  alterações	
  do	
  
potencial	
  da	
  membrana?	
  
Berne & Levy 
Principles of Physiology 4ª Ed (1996) 
Chemoreceptor 
Mechanoreceptor 
Photoreceptor 
Channel 
Gate closed 
Receptor 
Stimulator Gate 
opened 
Channel closed Channel open 
Photon 
Distenção 
16 
Fisiologia Animal 
Transdução	
  Sensorial	
  
Neurónio sensorial 
Corpúsculo 
de Pacini 
(pele) 
SNC (medula espinhal) 
Rhoades & Pflanzer (1996) Human Physiology (3ª Ed) 
Fisiologia Animal 
Transdução Sensorial 
Estímulo Alteração de permeabilidade 
Potencial 
receptor 
Potencial 
de acção 
17 
Fisiologia Animal 
Alterações	
  do	
  potencial	
  da	
  membrana	
  após	
  
esMmulação	
  da	
  célula	
  
Moffett et al. (1993) Human Physiology (2ª Ed)Potencial de 
acção 
Potenciais graduais 
Tempo 
Po
te
nc
ia
l d
e 
m
em
br
an
a 
 (m
V)
 
Estímulos 
-90 
-70 
0 
+60 (ENa) 
(EK) 
Potencial limiar 
Fisiologia Animal 
Potenciais	
  graduais	
  
Silverthorn, Human physiology (2001) 2 ed. 
18 
Fisiologia Animal 
Potenciais	
  graduais	
  
Silverthorn, Human physiology (2011) 5 ed. 
Fisiologia Animal 
Canal	
  iónico	
  sensível	
  à	
  voltagem 
 
19 
Fisiologia Animal 
O	
  potencial	
  de	
  
acção	
  
Fisiologia Animal 
Campbell N.A. (1999) Biology (4ª Ed) 
20 
Fisiologia Animal 
O	
  potencial	
  de	
  acção	
  
Fisiologia Animal 
Alterações	
  da	
  permeabilidade	
  da	
  membrana	
  a	
  Na+	
  e	
  K+	
  
responsáveis	
  pelo	
  potencial	
  de	
  acção 
 
21 
Fisiologia Animal 
Movimento	
  dos	
  iões	
  durante	
  o	
  PA	
  
Fisiologia Animal 
Período	
  refratário	
  
22 
Fisiologia Animal 
Potenciais	
  de	
  ação	
  
Tudo	
  ou	
  nada	
  
Fisiologia Animal 
Codificação	
  da	
  intensidade	
  do	
  
esOmulo	
  
23 
Fisiologia Animal 
Codificação	
  da	
  intensidade	
  do	
  esOmulo	
  
1 
2 
Rhoades & Pflanzer. Human Physiology (3ª Ed) 
Fisiologia Animal 
Especialização	
  funcional	
  do	
  neurónio	
  
sensorial	
  
Moffett et al. (1993) Human Physiology (2ª Ed) 
Voltage-gated channels 
Stimulus-gated 
channels 
Stimulus 
Stimulus 
M
em
br
an
e 
Po
te
nt
ia
l 
Time 
A 
Time 
Stimulus 
M
em
br
an
e 
Po
te
nt
ia
l 
B Receptor potential Action potentials 
24 
Fisiologia Animal 
Propagação	
  do	
  potencial	
  de	
  acção	
  
Purves et al, LIFE: The Science of Biology, 5ª Ed (1998) 
Fisiologia Animal 
Propagação	
  do	
  potencial	
  de	
  acção	
  
25 
Fisiologia Animal 
Velocidade	
  de	
  propagação	
  do	
  
potencial	
  de	
  acção	
  
•  Diâmetro	
  dos	
  axónios	
  
–  Maior	
  diâmetro	
  ⇒	
  Maior	
  velocidade	
  
	
  
Diâmetro Velocidade Exemplo 
(µm) (m/s) 
12-22 70-120 N. Sensoriais – posição dos músculos 
3-8 15-40 N. Sensoriais – tacto, pressão 
0,3-1,3 0,7-2,2 S. N. autonómico 
Fisiologia Animal 
Axónios	
  mielinizados	
  
Bainha de mielina 
Axónio 
Célula de 
Schwann 
Oligodendrócito 
Nódulo de 
Ranvier 
Núcleo 
SNP SNC 
26 
Fisiologia Animal Purves et al, LIFE: The Science of Biology, 5ª Ed (1998) 
Condução	
  saltatória	
  do	
  potencial	
  de	
  acção	
  nos	
  axónios	
  
mielinizados	
  
Fisiologia Animal 
27 
Fisiologia Animal 
Condução	
  do	
  PA	
  
Fisiologia Animal 
Comunicação	
  
entre	
  as	
  células	
  
Stimulus 
Receptor potential 
(graded) 
Action potentials 
(all-or-none) 
Synaptic potential 
(graded) 
Action potentials 
(all-or-none) 
Synaptic potential 
(graded) 
CNS 
Terminais sensoriais 
Segmento inicial 
do axónio 
28 
Fisiologia Animal 
Experiência	
  de	
  Loewi	
  
Porquê?	
  
Fisiologia Animal 
Comunicação	
  no	
  SN	
  
Sinapse	
  química	
  Sinapse	
  eléctrica	
  
29 
Fisiologia Animal 
Fox (2011) Human Physiology (12ª Ed) 
Gap	
  juncMons	
  
(Junções	
  de	
  hiato)	
  
Mitochondria
Synaptic
vesicles
Synaptic
cleft
Postsynaptic
cell (skeletal
muscle)
Terminal
bouton of 
axon
Figure 7.22 An electron micrograph of a chemical 
synapse. This synapse between the axon of a somatic motor 
neuron and a skeletal muscle cell shows the synaptic vesicles at 
the end of the axon and the synaptic cleft. The synaptic vesicles 
contain the neurotransmitter chemical.
Cytoplasm
Connexin
proteins
forming
gap
junctions
Cytoplasm
Two cells,
interconnected
by gap 
junctions
Plasma 
membrane
of one cell
Plasma 
membrane
of adjacent 
cell
Figure 7.21 The structure of gap junctions. Gap 
junctions are water-filled channels through which ions can pass 
from one cell to another. This permits impulses to be conducted 
directly from one cell to another. Each gap junction is composed 
of connexin proteins. Six connexin proteins in one plasma 
membrane line up with six connexin proteins in the other plasma 
membrane to form each gap junction.
179The Nervous System
heart. He had isolated the heart of a frog and, while stimulat-
ing the branch of the vagus that innervates the heart, per-
fused the heart with an isotonic salt solution. Stimulation 
of the vagus nerve was known to slow the heart rate. After 
stimulating the vagus nerve to this frog heart, Loewi col-
lected the isotonic salt solution and then gave it to a second 
heart. The vagus nerve to this second heart was not stimu-
lated, but the isotonic solution from the first heart caused the 
second heart to also slow its beat. 
 Loewi concluded that the nerve endings of the vagus 
must have released a chemical—which he called Vagusstoff —
that inhibited the heart rate. This chemical was subsequently 
identified as acetylcholine, or ACh. In the decades follow-
ing Loewi’s discovery, many other examples of chemical syn-
apses were discovered, and the theory of electrical synaptic 
transmission fell into disrepute. More recent evidence, ironi-
cally, has shown that electrical synapses do exist in the ner-
vous system (though they are the exception), within smooth 
muscles, and between cardiac cells in the heart. 
 Electrical Synapses: 
Gap Junctions 
 In order for two cells to be electrically coupled, they must 
be approximately equal in size and they must be joined by 
areas of contact with low electrical resistance. In this way, 
impulses can be regenerated from one cell to the next with-
out interruption. Adjacent cells that are electrically coupled 
are joined together by gap junctions. In gap junctions, the 
membranes of the two cells are separated by only 2 nano-
meters (1 nano meter = 10 − 9 meter). A surface view of 
gap junctions in the electron microscope reveals hexagonal 
arrays of particles that function as channels through which 
ions and molecules may pass from one cell to the next. Each 
gap junction is now known to be composed of 12 proteins 
known as connexins, which are arranged like staves of a bar-
rel to form a water-filled pore ( fig. 7.21 ). 
 Gap junctions are present in cardiac muscle, where they 
allow action potentials to spread from cell to cell, so that the 
myocardium can contract as a unit. Similarly, gap junctions 
in some smooth muscles allow many cells to be stimulated 
and contract together, producing a stronger contraction (as 
in the uterus during labor). The function of gap junctions 
in the nervous system is less well understood; neverthe-
less, gap junctions are found between neurons in the brain, 
where they can synchronize the firing of groups of neurons. 
Gap junctions are also found between neuroglial cells, where 
they are believed to allow the passage of Ca 2 + and perhaps 
other ions and molecules between the connected cells.
The function of gap junctions is more complex than was 
once thought. Neurotransmitters and other stimuli, acting 
through second messengers such as cAMP or Ca 2 +, can lead 
to the phosphorylation or dephosphorylation of gap junc-
tion connexin proteins, causing the opening or closing of 
gap junction channels. For example, light causes the ion 
 conductance through the gap junctions between neurons 
in the retina to increase in some neurons and decrease in 
others. 
 Chemical Synapses 
 Transmission across the majority of synapses in the ner-
vous system is one-way and occurs through the release of 
chemical neurotransmittersfrom presynaptic axon endings. 
These presynaptic endings, called terminal boutons (from 
the Middle French bouton = button) because of their swol-
len appearance, are separated from the postsynaptic cell by 
a synaptic cleft so narrow (about 10 nm) that it can be seen 
clearly only with an electron microscope ( fig. 7.22 ). 
fox78119_ch07_160-202.indd 179fox78119_ch07_160-202.indd 179 25/06/10 9:13 PM25/06/10 9:13 PM
Fisiologia Animal 
Sinapses	
  químicas	
  e	
  eléctricas	
  
Propriedade Sinapse	
  electrica Sinapse	
  química 
Distancia	
  entre	
  as	
  
membranas	
  pré-­‐	
  e	
  pós-­‐
sinapgca 
3	
  nm 30-­‐50	
  nm 
Congnuidade	
  
citoplasmágca 
Sim Não 
Componentes	
  
ultraestruturais 
Canais	
  “gap	
  juncgons” Zonas	
  acgvas,	
  vesículas	
  
e	
  receptores 
Agente	
  de	
  transmissão Corrente	
  eléctrica Mensageiro	
  químico 
Atraso	
  sinapgco Quase	
  nulo 0,3	
  -­‐	
  5	
  ms 
Direção	
  da	
  transmissão Bidireccional Unidireccional 
30 
Fisiologia Animal 
Sinapse	
  química	
  
Fisiologia Animal 
Proteínas	
  
sinápMcas	
  
31 
Fisiologia Animal 
 
 
Amino Acids Amines Peptides 
Gamma-amino butyric acid 
(GABA) 
Acetylcholine (ACh) Cholecystokinin (CCK) 
Glutamate (Glu) Dopamine (DA) Dynorphin 
Glycine (Gly) Epinephrine Enkephalins (Enk) 
Aspartate (Asp) Histamine Neuropeptide Y 
 Norepinephrine (NE) Somatostatin 
 Serotonin (5-HT) Substance P 
 Thyrotropin-releasing 
hormone 
 Vasoactive intestinal 
peptide (VIP) 
 
 
 
Glu	
   GABA	
  
ACh	
   NE	
  
Substance	
  P	
  
Os	
  principais	
  neurotransmissores	
  
Fisiologia Animal 
O	
  “ciclo”	
  da	
  ACh	
  
32 
Fisiologia Animal 
1. Channel closed until
 neurotransmitter
 binds to it
2. Open channel 
 permits diffusion of
 specific ions
(b)
Acetylcholine
Cytoplasm
Plasma
membrane
Ion
channel
Nicotinic ACh
receptors
(a)
Extracellular Fluid
Binding
site
Na+
K+
Figure 7.26 Nicotinic acetylcholine (ACh) receptors also function as ion channels. The nicotinic acetylcholine receptor 
contains a channel that is closed (a) until the receptor binds to ACh. (b) Na+ and K+ diffuse simultaneously, and in opposite directions, 
through the open ion channel. The electrochemical gradient for Na+ is greater than for K+, so that the effect of the inward diffusion of Na+ 
predominates, resulting in a depolarization known as an excitatory postsynaptic potential (EPSP).
184 Chapter 7
Table 7.4 | Comparison of Action Potentials and Excitatory Postsynaptic Potentials (EPSPs)
Characteristic Action Potential Excitatory Postsynaptic Potential
Stimulus for opening of ionic gates Depolarization Acetylcholine (ACh) or other excitatory 
neurotransmitter
Initial effect of stimulus Na+ channels open Common channels for Na+ and K+ open
Cause of repolarization Opening of K+ gates Loss of intracellular positive charges with time 
and distance
Conduction distance Regenerated over length of the axon 1–2 mm; a localized potential
Positive feedback between depolarization 
and opening of Na+ gates
Yes No
Maximum depolarization + 40 mV Close to zero
Summation No summation—all-or-none event Summation of EPSPs, producing graded 
depolarizations
Refractory period Yes No
Effect of drugs ACh effects inhibited by tetrodotoxin, 
not by curare
ACh effects inhibited by curare, not by 
tetrodotoxin
fox78119_ch07_160-202.indd 184fox78119_ch07_160-202.indd 184 25/06/10 9:13 PM25/06/10 9:13 PM
Fox (2011) Human Physiology (12ª Ed) 
Receptores	
  nicoOnicos	
  para	
  a	
  ACh	
  
Fisiologia Animal Fox (2011) Human Physiology (12ª Ed) 
Receptores	
  muscarínicos	
  para	
  a	
  ACh	
  
185The Nervous System
the nicotinic receptors, these receptors do not contain ion 
channels. The ion channels are separate proteins located 
at some distance from the muscarinic receptors. Binding of 
ACh (the ligand) to the muscarinic receptor causes it to acti-
vate a complex of proteins in the cell membrane known as 
G-proteins —so named because their activity is influenced 
by guanosine nucleotides (GDP and GTP). This topic was 
introduced in chapter 6, section 6.5. 
 There are three G-protein subunits, designated alpha, 
beta, and gamma. In response to the binding of ACh to its 
receptor, the alpha subunit dissociates from the other two 
subunits, which stick together to form a beta-gamma com-
plex. Depending on the specific case, either the alpha subunit 
or the beta-gamma complex then diffuses through the mem-
brane until it binds to an ion channel, causing the channel 
to open or close ( fig. 7.27 ). A short time later, the G-protein 
ACh
G-proteins K+ channel
Plasma membrane
K+
K+
Receptor
1. ACh binds
 to receptor
2. G-protein
 subunit
 dissociates
3. G-protein
 binds to K+
 channel,
 causing it
 to open
Figure 7.27 Muscarinic ACh receptors require the action of G-proteins. The figure depicts the effects of ACh on the 
pacemaker cells of the heart. Binding of ACh to its muscarinic receptor causes the beta-gamma subunits to dissociate from the alpha 
subunit. The beta-gamma complex of G-proteins then binds to a K+ channel, causing it to open. Outward diffusion of K+ results, slowing 
the heart rate.
Drug Origin Effects
Botulinum toxin Produced by Clostridium botulinum (bacteria) Inhibits release of acetylcholine (ACh)
Curare Resin from a South American tree Prevents interaction of ACh with its nicotinic receptor proteins
α-Bungarotoxin Venom of Bungarus snakes Binds to ACh receptor proteins and prevents ACh from binding
Saxitoxin Red tide (Gonyaulax) algae Blocks voltage-gated Na+ channels
Tetrodotoxin Pufferfish Blocks voltage-gated Na+ channels
Nerve gas Artificial Inhibits acetylcholinesterase in postsynaptic membrane
Neostigmine Nigerian bean Inhibits acetylcholinesterase in postsynaptic membrane
Strychnine Seeds of an Asian tree Prevents IPSPs in spinal cord that inhibit contraction of antagonistic muscles
Table 7.5 | Drugs That Affect the Neural Control of Skeletal Muscles
Case Investigation CLUES
Sandra experienced severe muscle weakness 
after eating just a little of the local shellfish gathered at the 
beginning of a red tide. Mussels and clams are filter feeders 
that concentrate the poison (saxitoxin) in the red tide.
■ How could saxitoxin produce Sandra’s muscle 
weakness?
■ Given that the diaphragm is a skeletal muscle, 
propose one mechanism by which paralytic shellfish 
poisoning could be fatal.
fox78119_ch07_160-202.indd 185fox78119_ch07_160-202.indd 185 25/06/10 9:13 PM25/06/10 9:13 PM
Nicotinic ACh
receptors
Postsynaptic membrane of
• All autonomic ganglia
• All neuromuscular junctions
• Some CNS pathways
Na+
ACh ACh ACh
K+
K+ K+
Depolarization
Excitation
Ligand-gated channels
(ion channels are part
of receptor)
Muscarinic ACh
receptors
• Produces parasympathetic nerve effects in
the heart, smooth muscles, and glands
• G-protein-coupled receptors (receptors
influence ion channels by means of G-proteins)
Hyperpolarization Depolarization
(K+ channels
opened)
(K+ channels
closed)
Inhibition
Produces slower
heart rate
Excitation
Causes smooth muscles of the
digestive tract to contract
Na+ or Ca2+
γ
βα γ
βα
Figure 9.11 Comparison of nicotinic and muscarinic acetylcholine receptors. Nicotinic receptors are ligand-gated, 
meaning that the ion channel (which runs through the receptor) is opened by binding to the neurotransmitter molecule (the ligand). The 
muscarinic ACh receptors are G-protein-coupled receptors, meaning that the binding of ACh to its receptor indirectly opens or closes ionchannels through the action of G-proteins.
 The effects of ACh in an organ depend on the nature of 
the cholinergic receptor ( fig. 9.11 ). As may be recalled from 
 chapter 7, there are two types of cholinergic receptors— nicotinic 
and muscarinic. Nicotine (derived from the tobacco plant), as 
well as ACh, stimulates the nicotinic ACh receptors. These are 
located in the neuromuscular junction of skeletal muscle fibers 
and in the autonomic ganglia. Nicotinic receptors are thus stim-
ulated by ACh released by somatic motor neurons and by pre-
ganglionic autonomic neurons. Muscarine (derived from some 
poisonous mushrooms), as well as ACh, stimulates the ACh 
receptors in the visceral organs. Muscarinic receptors are thus 
stimulated by ACh released by postganglionic parasympathetic 
axons to produce the parasympathetic effects. Nicotinic and 
muscarinic receptors are further distinguished by the action of 
the drugs curare (tubocurarine), which specifically blocks the 
nicotinic ACh receptors, and atropine (or belladonna ), which 
specifically blocks the muscarinic ACh receptors. 
 As described in chapter 7, the nicotinic ACh receptors 
are ligand-gated ion channels. That is, binding to ACh causes 
the ion channel to open within the receptor protein. This 
allows Na + to diffuse inward and K + to diffuse outward. 
However, the Na + gradient is steeper than the K + gradient, 
and so the net effect is a depolarization. As a result, nico-
tinic ACh receptors are always excitatory. In contrast, mus-
carinic ACh receptors are coupled to G-proteins, which can 
then close or open different membrane channels and activate 
CLIN ICAL APPL ICATION
The muscarinic effects of ACh are specifically inhibited by the 
drug atropine, derived from the deadly nightshade plant 
(Atropa belladonna). Indeed, extracts of this plant were used 
by women during the Middle Ages to dilate their pupils 
( atropine inhibits parasympathetic stimulation of the iris). This 
was thought to enhance their beauty (in Italian, bella = beauti-
ful, donna = woman). Atropine is used clinically today to dilate 
pupils during eye examinations, to reduce secretions of the 
respiratory tract prior to general anesthesia, to inhibit spas-
modic contractions of the lower digestive tract, and to inhibit 
stomach acid secretion in a person with gastritis. Atropine is 
also given intramuscularly to treat exposure to nerve gas, 
which inhibits acetylcholinesterase and thereby increases syn-
aptic transmission at both nicotinic and muscarinic ACh recep-
tors. Atropine blocks the muscarinic effects of nerve gas, 
which include increased mucous secretions of the respiratory 
tract and muscular spasms in the pulmonary airways.
different membrane enzymes. As a result, their effects can be 
either excitatory or inhibitory ( fig. 9.11 ). 
 Scientists have identified five different subtypes of musca-
rinic receptors (M 1 through M 5 ; table 9.6 ). Some of these cause 
contraction of smooth muscles and secretion of glands, while 
253The Autonomic Ner vous System
fox78119_ch09_239-262.indd 253fox78119_ch09_239-262.indd 253 02/07/10 7:02 PM02/07/10 7:02 PM
33 
Fisiologia Animal 
Acetilcolina 
Curare Atropina 
Muscarina Nicotina Agonistas 
Antagonistas 
Receptor 
nicotínico 
Receptor 
muscarínico 
Bear et al. Neuroscience: Exploring the Brain (1996) 
Agonistas	
  e	
  antagonistas	
  do	
  AChR	
  
Fisiologia Animal 
InacMvação	
  dos	
  neurotransmissores	
  
34 
Fisiologia Animal 
Substâncias	
  que	
  afectam	
  	
  
a	
  transmissão	
  nervosa	
  
•  Toxina	
  do	
  botulismo	
  
–  Bactéria	
  (Clostridium	
  botulinum)	
  
–  Inibe	
  a	
  libertação	
  de	
  ACh	
  (NT)	
  
•  Curare	
  
–  Resina	
  de	
  arvore	
  
–  Bloqueia	
  receptor	
  para	
  a	
  ACh	
  
•  	
  α-­‐Bungarotoxina	
  
–  Veneno	
  de	
  cobra	
  
–  Bloqueia	
  receptor	
  para	
  a	
  ACh	
  
•  Tetrodotoxina	
  
–  Peixe	
  japonês	
  (Fugu)	
  
–  Bloqueia	
  o	
  impulso	
  nervoso	
  
•  Gás	
  dos	
  nervos	
  
–  Feijão	
  nigeriano	
  
–  Inibe	
  a	
  aceglcolinesterase	
  
•  Alprazolam	
  
–  Xanax	
  
hp://www.watchcartoononline.com/the-­‐simpsons-­‐episode-­‐211-­‐one-­‐fish	
  
Fisiologia Animal 
Sinapse excitatória Sinapse inibitória 
↑PK+ ou ↑PCl- ↑PNa+ 
PIPS PEPS 
Vander	
  et	
  al.	
  Human	
  Physiology	
  (8ª	
  Ed)	
  
Sinapses	
  excitatórias	
  e	
  inibitórias	
  
Vander et al.: Human 
Physiology: The 
Mechanism of Body 
Function, Eighth Edition
II. Biological Control 
Systems
8. Neural Control 
Mechanisms
© The McGraw−Hill 
Companies, 2001
Via the local current mechanisms described ear-
lier, the plasma membrane of the entire postsynaptic
cell body and the initial segment reflect the changes
at the postsynaptic membrane. The membrane of a
large area of the cell becomes slightly depolarized dur-
ing activation of an excitatory synapse and slightly hy-
perpolarized or stabilized during activation of an in-
hibitory synapse, although these graded potentials
will decrease with distance from the synaptic junction
(Figure 8–31).
In the previous examples, we referred to the thresh-
old of the postsynaptic neuron as though it were the
same for all parts of the cell. However, different parts
of the neuron have different thresholds. In many cells
the initial segment has a lower threshold (that is, much
closer to the resting potential) than the threshold of the
cell body and dendrites. In these cells the initial seg-
ment reaches threshold first whenever enough EPSPs
summate, and the resulting action potential is then
propagated from this point down the axon (and, some-
times, back over the cell body and dendrites).
The fact that the initial segment usually has the
lowest threshold explains why the location of individ-
ual synapses on the postsynaptic cell is important. A
synapse located near the initial segment will produce
a greater voltage change there than will a synapse on
the outermost branch of a dendrite because it will ex-
pose the initial segment to a larger local current. In fact,
some dendrites use propagated action potentials over
portions of their length to convey information about
the synaptic events occurring at their endings to the
initial segment of the cell.
Postsynaptic potentials last much longer than ac-
tion potentials. In the event that cumulative EPSPs
cause the initial segment to still be depolarized to
threshold after an action potential has been fired and
the refractory period is over, a second action potential
will occur. In fact, as long as the membrane is depo-
larized to threshold, action potentials will continue to
arise. Neuronal responses at synapses almost always
occur in bursts of action potentials rather than as sin-
gle isolated events.
Synaptic Effectiveness
Individual synaptic events—whether excitatory or in-
hibitory—have been presented as though their effects
are constant and reproducible. Actually, the variability
in postsynaptic potentials following any particular
presynaptic input is enormous. The effectiveness of a
given synapse can be influenced by both presynaptic
and postsynaptic mechanisms.
First, a presynaptic terminal does not release a con-
stant amount of neurotransmitter every time it is acti-
vated. One reason for this variation involves calcium
concentration. Calcium that has entered the terminal
during previous action potentials is pumped out of the
cell or (temporarily) into intracellular organelles. If cal-
cium removal does not keep up with entry, as can oc-
cur during high-frequency stimulation, calcium con-
centration in the terminal, and hence the amount of
neurotransmitter released upon subsequent stimula-
tion, will be greaterthan usual. The greater the amount
of neurotransmitter released, the greater the number
of ion channels opened (or closed) in the postsynaptic
membrane, and the larger the amplitude of the EPSP
or IPSP in the postsynaptic cell.
The neurotransmitter output of some presynaptic
terminals is also altered by activation of membrane re-
ceptors in the terminals themselves. These presynaptic
receptors are often associated with a second synaptic
ending known as an axon-axon synapse, or presynap-
tic synapse, in which an axon terminal of one neuron
ends on an axon terminal of another. For example, in
Figure 8–32 the neurotransmitter released by A com-
bines with receptors on B, resulting in a change in the
202 PART TWO Biological Control Systems
Time
Time
M
em
br
an
e 
po
te
nt
ia
l
Initial segment
Initial segment
M
em
br
an
e 
po
te
nt
ia
l
M
em
br
an
e 
po
te
nt
ia
l
Time
Time
Initial segment
Initial segment
(a) Excitatory synapse
(b) Inhibitory synapse
+
+
++ +
+
+
+
+
+ +
+ +
+
+
+
+
+
FIGURE 8–31
Comparison of excitatory and inhibitory synapses, showing
current direction through the postsynaptic cell following
synaptic activation. (a) Current through the postsynaptic cell
is away from the excitatory synapse, depolarizing the initial
segment. (b) Current through the postsynaptic cell
hyperpolarizes the initial segment.
Vander et al.: Human 
Physiology: The 
Mechanism of Body 
Function, Eighth Edition
II. Biological Control 
Systems
8. Neural Control 
Mechanisms
© The McGraw−Hill 
Companies, 2001
Via the local current mechanisms described ear-
lier, the plasma membrane of the entire postsynaptic
cell body and the initial segment reflect the changes
at the postsynaptic membrane. The membrane of a
large area of the cell becomes slightly depolarized dur-
ing activation of an excitatory synapse and slightly hy-
perpolarized or stabilized during activation of an in-
hibitory synapse, although these graded potentials
will decrease with distance from the synaptic junction
(Figure 8–31).
In the previous examples, we referred to the thresh-
old of the postsynaptic neuron as though it were the
same for all parts of the cell. However, different parts
of the neuron have different thresholds. In many cells
the initial segment has a lower threshold (that is, much
closer to the resting potential) than the threshold of the
cell body and dendrites. In these cells the initial seg-
ment reaches threshold first whenever enough EPSPs
summate, and the resulting action potential is then
propagated from this point down the axon (and, some-
times, back over the cell body and dendrites).
The fact that the initial segment usually has the
lowest threshold explains why the location of individ-
ual synapses on the postsynaptic cell is important. A
synapse located near the initial segment will produce
a greater voltage change there than will a synapse on
the outermost branch of a dendrite because it will ex-
pose the initial segment to a larger local current. In fact,
some dendrites use propagated action potentials over
portions of their length to convey information about
the synaptic events occurring at their endings to the
initial segment of the cell.
Postsynaptic potentials last much longer than ac-
tion potentials. In the event that cumulative EPSPs
cause the initial segment to still be depolarized to
threshold after an action potential has been fired and
the refractory period is over, a second action potential
will occur. In fact, as long as the membrane is depo-
larized to threshold, action potentials will continue to
arise. Neuronal responses at synapses almost always
occur in bursts of action potentials rather than as sin-
gle isolated events.
Synaptic Effectiveness
Individual synaptic events—whether excitatory or in-
hibitory—have been presented as though their effects
are constant and reproducible. Actually, the variability
in postsynaptic potentials following any particular
presynaptic input is enormous. The effectiveness of a
given synapse can be influenced by both presynaptic
and postsynaptic mechanisms.
First, a presynaptic terminal does not release a con-
stant amount of neurotransmitter every time it is acti-
vated. One reason for this variation involves calcium
concentration. Calcium that has entered the terminal
during previous action potentials is pumped out of the
cell or (temporarily) into intracellular organelles. If cal-
cium removal does not keep up with entry, as can oc-
cur during high-frequency stimulation, calcium con-
centration in the terminal, and hence the amount of
neurotransmitter released upon subsequent stimula-
tion, will be greater than usual. The greater the amount
of neurotransmitter released, the greater the number
of ion channels opened (or closed) in the postsynaptic
membrane, and the larger the amplitude of the EPSP
or IPSP in the postsynaptic cell.
The neurotransmitter output of some presynaptic
terminals is also altered by activation of membrane re-
ceptors in the terminals themselves. These presynaptic
receptors are often associated with a second synaptic
ending known as an axon-axon synapse, or presynap-
tic synapse, in which an axon terminal of one neuron
ends on an axon terminal of another. For example, in
Figure 8–32 the neurotransmitter released by A com-
bines with receptors on B, resulting in a change in the
202 PART TWO Biological Control Systems
Time
Time
M
em
br
an
e 
po
te
nt
ia
l
Initial segment
Initial segment
M
em
br
an
e 
po
te
nt
ia
l
M
em
br
an
e 
po
te
nt
ia
l
Time
Time
Initial segment
Initial segment
(a) Excitatory synapse
(b) Inhibitory synapse
+
+
++ +
+
+
+
+
+ +
+ +
+
+
+
+
+
FIGURE 8–31
Comparison of excitatory and inhibitory synapses, showing
current direction through the postsynaptic cell following
synaptic activation. (a) Current through the postsynaptic cell
is away from the excitatory synapse, depolarizing the initial
segment. (b) Current through the postsynaptic cell
hyperpolarizes the initial segment.
35 
Fisiologia Animal 
Integração	
  dos	
  impulsos	
  nervosos	
  
Campbell N.A. (2000) Biology (5ª Ed) 
Fisiologia Animal Campbell N.A. (1999) Biology (4ª Ed) 
Somação	
  dos	
  potencias	
  pós-­‐sinapMcos	
  
36 
Fisiologia Animal 
Pós Pré (excitador) 
Pré 
(inibidor) 
1 
2 
1 
Pós 
Pós 
Pós 
1 
2 
2 
Moffett et al. (1993) Human Physiology (2ª Ed) 
Integração	
  sinápMca	
  
Fisiologia Animal 
Segmento 
inicial 
Excitador 
Inibidor 
Tempo 
Segmento inicial 
Limiar 
Vo
lta
ge
m
 
Axónio 
Vo
lta
ge
m
 
Moffett et al. (1993) Human Physiology (2ª Ed) 
Integração	
  sinápMca	
  
37 
Fisiologia Animal