BIO 122 LECTURE 3: NEUROMUSCULAR PHYSIOLOGY

I.

SIGNALLING IN NERVES

NERVE IMPULSE
transmission of action potential from the axon hillock to the
axon terminals and into the adjacent neuron
action potential = all or nothing; does not diminish based
on distance from origin
action potentials jump from node to node
unmyelinated vs. myelinated nerve fibers (voltage-gated
Na+ channels are present only at the nodes of Ranvier)
Why action potential jump down axon
1.
2.
3.

As charge spreads down an axon, myelination (Schwann

cells) prevents ion from leaking out the PM.
Charge spreads unimpeded until it reaches an unmyelinated
section of the axon (node of Ranvier, which is packed with
Na+ channels)
Electrical signals continue to jump down the axon much
faster than down an unmyelinated cell.

Normal conduction of myelinated fibers high density voltagegated Na+ channel at node; saltatory conduction of signal
Demyelination of nerve fibers in MS increased Na+ channels
along demyelinated axons (multiple sclerosis)
SYNAPSE
Charles Sherrington, 1897
specialized intercellular spaces between a neuron and an
effector cell or another neuron
synaptic transmission vs. axonal transmission
presynaptic and postsynaptic terminals
1.

2.

Electrical Synapse
occurs in gap junction (nexus) present
transmission occurs without measurable delay
little or no fluctuation in AP (continuous)
gap junction are formed exclusively from hexameric
pores (connexons) = connect cells with each other for
robust electrical coupling
functions: metabolic (diffusional exchange); local
inhibitory network in CNS
Chemical Synapse
most common synaptic transmission
synaptic cleft: 20 to 50 nm
time lag occurs
AP may fluctuate
mediated by NEUROTRANSMITTERS (from
terminal bulb of presynaptic axon)

synthesized by neuron (1 neuron : 1 transmitter

type)

present in presynaptic terminals

bind to specific receptor on postsynaptic

membrane

associated with specific mechanisms of

deactivation

e.g. Ach and Ne

no. of vesicles is reduced with:
decreased Ca2+ and Na+ in ECF
previous depolarization making the AP weaker

J4R4FFE

Synaptic Transmitter at Neuromuscular Junction (NMJ):

Acetylcholine Synthetic and Storage
-

Quantum: amount of neurotransmitters in one vesicle that

determines the minimum size of postsynaptic potential; e.g.
Ach = quantal units of 3000 molecules
*cholinergic vesicle = ~103 molecules of Ach
Quantal release = transmitter is released in quantum (there
is a certain amount that is released)
miniature EPSPs (mEPSPs) change in the membrane
potential of a muscle cell produced by a single quantum
mEPSPs EPSP threshold AP to postsynaptic
terminal
normal neurotransmission requires the release of many
vesicle simultaneously
regulated fusion of synaptic vesicles with the nerve
terminals and release of neurotransmitter to synaptic cleft:
docking priming fusion

SYNAPTIC POTENTIAL
generated during the transmission of a nerve impulse across
a synapse
graded, with longer duration but lower amplitude (unlike
AP which is all-or-none)
magnitude related to amount of neurotransmitter released
1.
2.

Presynaptic Potential AP arriving at the terminal end of

an axon
Postsynaptic Potential
a. EPSP
depolarization leads to an AP resulting from
opening of ligand-gated ion channels
permeability changes generating EPSP are
VOLTAGE-INDEPENDENT, instead are
TRANSMITTER-DEPENDENT
e.g. Na+ ions flow inward generates EPSP
increases postsynaptic potential
depolarization
b. IPSP
tends to hyperpolarize so that AP is not
generated
e.g. Cl- ions flow inward and/or K+ ions flow
outward (membrane is simultaneously
permeable to Cl- and K+ ions) generates
IPSP
decreases postsynaptic potential
hyperpolarization

Multiple excitatory and inhibitory inputs onto dendrites and the

soma SUMMATE EPSP + IPSP.
Spatial Summation
several neurons
stimulating at the same time
occurs at different sites of
membrane

Temporal Summation
single neuron
stimulating at different times
occurs at the same site of
membrane

DENDRITES
unable to transmit AP due to:

few voltage-gated channels

too high threshold for excitation

transmit ELECTRONIC CURRENT down to the soma
dendrites are long with thin membranes at least partially
permeable to K+ and Cl- leaky to electric current
decremental conduction (not saltatory)
current spreads bc fluid (without generation of AP)
dendrites summate the excitatory and inhibitory potentials

Termination of Synaptic Transmission

resorption (active reuptake) of neurotransmitter or its
breakdown products
enzymatic degradation of neurotransmitter (e.g.
Acetylcholinesterase)
Pre and Postsynaptic Inhibitions

NMJ vs. Neuron-neuron Synapse

NMJ = more powerful synapses; AP in motor neuron
produces AP at target muscle fiber
N-N = require simultaneous inputs from presynaptic
neurons to generate AP to postsynaptic neuron

b.

Depression
decrease in amplitude of PSPs with successive
presynaptic impulses
basis for occurrence of habituation (decreased
intensity of an effector response)

Synaptic Plasticity
changes in synaptic efficacy over time
amplitudes of synaptic potentials are not constant over time
a. Facilitation
increase in amplitude of PSPs in response to
successive presynaptic impulses
basis of occurrence of sensitization (increased
intensity of an effector response)

II.

SENSORY RECEPTION

Receptor Cell
specialized cell responsive to internal and external stimuli
has the ability to convert energy into neural signal
stimulus receptor afferent nerve CNS

RECEPTOR POTENTIAL
graded depolarizartion of a receptor in response to
stimulation
ionic basis: increased permeability of receptor membrane to
all small ions, esp to Na+

Adaptation Curves (Examples)

Characteristics:
1.

An adequate stimulus elicits a graded RP, the amplitude of

which is a function of stimulus intensity
Adequate stimulus form of stimulus energy to which the
receptor is most sensitive or to where it normally responds

2.

The frequency of resultant AP in a receptor is a coded

representation of the intensity of the adequate stimulus

Receptor potential is graded and non-propagated.

Action potential is non-graded and propagated.
1.

2.

3.

4.
Sensory Transduction:
absorption of stimulus energy (SE) transduction of SE to electrical
signal amplification of energy integration and conduction
Sensory Reception and Processing:
stimulus sense organ (accessory structure) transducer (sensory
cells) action potential (nerve transmission) decoder (CNS)
TRANSDUCTION: Excitation of Receptors to Generate RP
Altered permeability of membrane to ions:
1. mechanical deformation of receptors
2. chemical application
3. temperature change
4. effects of electromagnetic radiation
Receptor Adaptation
decrease in the response of a receptor to a steadily
maintained stimulus over time
decrease in firing of AP despite maintained depolarization
Types:
1. Tonic Receptors slowly adapting; respond for the
duration of the stimulus
2. Phasic Receptors radily adapting; adapts to a
constant stimulus and turn off

5.

Muscle spindle receptors

sensory neurons that detect change in muscle length
intrafusal muscle fibers distributed among extrafusal
ion channels connected by spectrin = responds to
membrane deformation/stretch
Inner hair cell transducers
auditory and vestibular apparatus
stereocilia and kinocilium (true for vestibular,
degenerate for auditory)
inner hair cells innervated by sensory + motor nerves
extracellular fluid (i.e. endolymph) around hair cells
= potassium-rich
tip link = connects stereocilia at one end to an ion
channel, one that admits potassium and calcium
depolarization = movement of cilia towards
kinocilium
Olfactory receptors
neurons that have ciliated terminal ends projected into
the mucus of olfactory epithelium
odorant receptors located in the cilia
each olfactory receptor cell expresses only one type
of odorant receptor = binding protein
Gustatory receptors
tongue papillae taste buds taste cell innervated
by sensory nerve
can be produced in different ways:
a. through cationic channels (Na+, Na+/H+
cotransport)
b. blocking of K+ channels
c. through secondary messengers that work close
to K+ channels (bitter and sweet)
d. through secondary messengers that open Cl- or
non-specific ion channel
Visual receptors
rods and cones of the retina
rhodopsin and cone pigments = light sensitive
chemicals found in the outer segment
light rhodopsin decomposition + hyperpolarization
of rod receptor potential (not depolarization)

Dark State
cGMP-gated Na+ channels,
which are open in the dark
membrane less negative
active transport of Na+
membrane more negative
RMP = -40 mV normal in dark
conditions

Light Stimulation
rhodopsin decomposition
cGMP-gated Na+ channels close
membrane more negative
hyperpolarization

III.
A.

MOVEMENT AND LOCOMOTION

SKELETAL MUSCLES

Skeletal Muscle Structure

muscle cells/muscle fiber
multinucleated; diameter = 10-80 m
several myofibrils (1-2 m) comprise each muscle fiber
sarcomere = functional unit of a myofibril

Drugs that cause muscle spasm

through Ach-like action
metacholine, carbachol, nicotine
destroyed very slowly by cholinesterase or not at all
through Ach-ase inactivation
neostigmine, physostigmine bind with Ach-ase for
several hours but reversible
diisopropyl fluorophosphates a nerve gas that binds with
Ach-ase for weeks (lethal)

Skeletal Muscle Innervation

motor unit: composed of motor neuron + all muscle cells
innervated
there are many motor units in a muscle
a single motor neuron may innervate several fibers

fewer muscle fibers per neuron the finer the

movement (e.g. fingers)

many muscle fibers per motor unit coarse

movement (e.g. trunk muscles)

Drugs that block transmission at NMJ

prevent impulse transmission
curariform drugs

Myofibrils
contain contractile elements of muscles
A band (dark band) thick filaments
M line center of the A band
I band (light band) thin filaments
Z line/disk center of I band

How is Ca2+ released from sarcoplasmic reticulum?

Myasthenia gravis
autoimmune disease where antibodies attack, block or alter
the Ach receptors at NMJ prevents muscle contraction
mostly affect voluntary muscles
muscle weakness

1.

Plunger Model
ryanodine receptors block Ca2+ channels
AP: calcium lifts the ryanodine

2.

Enzyme- or messenger-mediated mechanism

Sarcomere
Z-M-Z
Z line -actinin/titin binds actin of adjacent sarcomeres
M line Mittel of sacromere
Myosin
composed of two coiled polypeptide chains
tails are oriented towards the center of the sarcomere (M
line)
Actin
-

composed of two coiled actin molecules + regulatory

proteins

TROPOMYOSIN = covers actin binding sites

TROPONIN = theww binding sites (for

tropomyosin, actin and Ca2+ ions)

EXCITATION

NMJ: Chemical Synapse Ach

CONTRACTION

RELAXATION

Sliding Filament Mechanism

decreases in width: sarcomere, I band, H zone
no change: A band, myosin and actin filaments

Contraction-Relaxation Steps Requiring ATP

splitting of ATP by myosin ATPase provides energy for
power stroke of cross bridge
binding of fresh molecule of ATP to myosin leads to cross
bridge detachment from actin filament at end of power
stroke so cycle can be repeated
active transport of Ca2+ back to sarcoplasmic reticulum
during relaxation
calsequestrin (in sarcoplasmic reticulum)
Isotonic Contractions
muscle shortens with constant
tension
load < tension
Slow Muscle Fibers
slow but prolonged response
slow contraction, longer duration
associated with smaller fibers
innervated by smaller nerves

Cross-Bridge Cycle

extensive blood supply and

mitochondria
high myoglobin red/dark
muscles
low levels of myosin ATPase
and glycolytic enzymes
Type I/Slow Oxidative =
depends on aerobic processes

B.

Isometric Contractions
muscle remains same length
during contraction; tension is
variable
load > tension
Fast Muscle Fibers
rapid contraction but short
response
extensive SR for rapid release of
Ca2+
associated with large fibers
which elicit great strength of
contraction
less extensive blood supply and
mitochondria
low myoglobin white muscles
high levels of myosin ATPase
and glycolytic enzymes
Type IIA/Fast Oxidative
Glycolytic (FOG) = intermediate
Type IIB/Fast Glycolytic =
anaerobic processes

SMOOTH MUSCLES

Smooth Muscle Structure

Energy Sources for Contraction

Main source = ATP
limited
must be regenerated through:

Direct Phosphorylation

creatine phosphate/phosphocreatine (CP)

high energy molecule found in muscle fibers

creatine phosphokinase transfers PO4 from CP

to ADP

no striations
no sarcomere
no troponin
no T-tubules
less developed SR

Smooth Muscle Innervation: Autonomic

no NMJ
neurotransmitters are released from varicosites

Types:
1.
2.
-

Multi-unit
one nerve per muscle cell neurogenic
e.g. muscles found in iris of eyes, trachea, arteries
Single-unit
one nerve + gap junctions myogenic
e.g. peristaltic wave in GI tract

Action Potential in Cardiac Myocyte

Smooth Muscle Contraction

1.
-

2.
-

C.

With excitation-contraction coupling

through neural input (autonomic nervous system)

Parasympathetic: Ach as NT binding with

muscarinic receptor

Sympathetic: NE as NT
Without E-C coupling
through hormones, paracrine agents (effects/signals
neighboring cells), etc. involving secondary messengers
CARDIAC MUSCLES

Dyhydropyrinidine receptors are unable to affect function of

ryanodine receptors,

Cardiac Muscle Structure

with striation
with troponin
with developed SR
with T-tubules

INTERCALATED DISCS + gap junctions (unique

feature)
regions of low electrical resistance for action potential
transmission
marks adjacent muscle cells
innervated by autonomic nervous system
myogenic
ECF + SR = calcium sources
Ach is inhibitory to contraction (vs. skeletal = induces
contraction)
NE is excitatory (responsible for fast heart rate)

instead, the release of large amounts of Ca2+ opens RyRs.

Smooth
contraction: Ca2+ binds with
calmodulin (vs. skeletal =
troponin)
contracts more slowly and
exhibit more prolonged
contraction with less ATP
relaxation: requires myosin
phosphatase enzyme to
dephosphorylate myosin

sources of Ca2+ are both

extracellular and intracellular
(SR)
extracellular Ca2+ allows
prolonged contraction
intracellular increase in Ca2+ =
due to nerve stimulation or
hormonal/local factors

Cardiac
excitation: requires both extra and
intracellular sources of Ca2+
contraction: mechanism is similar
to skeletal but more calcium is
released for AP generation more
actin-myosin interaction = to avoid
tetany of heart
relaxation:
1. active transport of Ca2+
back into SR during
relaxation
2. 3 Na : 1 Ca antiport in
SR and sarcolemmal
pump

Thick Filament Regulation (Phosphorylation of Myosin):

calmodulin + Ca2+ activates myosin light-chain kinase (MLK)
adds phosphate to myosin phosphorylated myosin binds to actin
contraction

Growth cone
developing axon (terminal portion) not yet synaptically
connected
guides the axon in looking for synaptic target
lamellipodium + filopodium + microfilaments

[vs. skeletal = Thin Filament Regulation]

depends on the uncovering of the thin filament (actin)

Addition of G-actin to F-actin

filopodium

D.

NON-MUSCLE CELLS

Cytoskeleton
network of protein filaments in eukaryotic cell cytoplasm
that provides shape, support and movement
cytomuslculature
Three types of protein filaments:
1. Actin Filaments (Microfilaments)
maintain cell shape by resisting tension (pull)
move cells via muscle contraction or cell crawling
divide animal cell into two
move organelles and cytoplasm in plants, fungi and
animals
2. Intermediate Filaments
maintain cell shape by resisting tension (pull)
anchor nucleus and some other organelles
3. Microtubules
maintain cell shape by resisting compression (push)
move cells via flagella or cilia
move chromosomes during cell division
move organelles
provide tracks for intracellular transport
Actin Filaments in Crawling Cells (Amoeboid)
1.
2.
3.

Trailing edge
where most actin is heavily distributed
Leading edge
pulls the cell forward
Stress fibers
lie on ventral surfaces of cells
made up of actin-myosin
form in response to tension generation within cell;
adhesion and deadhesion of cell to substratum

Contractile bundle
stress fibers
Cell cortex
gel
beneath the PM
actin-myosin
support + stiffens the fluid-like (gel) membrane
randomly arranged
Filopodium
thinner projections of cells
actins are tightly arranged in parallel bundle

Cells with amoeboid movement

of amoebas
embryonic cells during development
invasion of tissues by leukocytes (macrophages)
migration of cells during wound-healing
metastasis of cancer cells
Actin-binding Proteins: -actin, Filamin, Fimbrin
determine the form + function of actin filaments

-actin = contractile bundles

filamin = gel

fimbrin = parallel bundles

Steps in Cell Crawling
1.
2.

3.

Protrusion
of the leading edge
polymerization of actin subunits to form actin fils
Adhesion
to certain substrates
mostly stress fibers contribute to adhesion
cortex, hindi humahaba pero nagmo-move
*Deadhesion trailing end
Traction
interaction of actin-myosin

Cytoplasmic Gel-Sol Conversion: Role in Locomotion

Gel-Sol
actin cytoskeleton transitioning between solid-like elastic
material (gel/gelation) and a solution-like viscous material
(sol/solation)
from gel to sol; gel at rest, sol for contraction
induced by presence of calcium

Axoneme in Cilia and Flagella

similarly organized
9+2 arrangement of microtubules
-tubules = 13 profilaments
-tubules = 11 profilaments
central = 13 profilaments
basal body = no central fils 9+0
radial spokes = linkages of outer doublets to central
nexins = links adjacent doublets
dyein arms

inner and outer

protein motor molecules that walk along adjacent

microtubules

ATPase activity:

hydrolysis of ATP associated with

reattachment of the dyein arms to the adjacent
-tubule but at a different location a sliding
motion of adjacent outer tubule structures

binding of ATP release of the dyein arms

from the adjacent -tubule

sliding microtubule

In a cilium/flagellum, two adjacent doublets cannot slide far because

they are physically restrained by proteins so they bend.
CILIA
-

occur in groups; shorter

power stroke: counters a force; cilium bends at the base
recovery stroke: bend propagates up the cilium (bottom to
top high energy)
motion with single bend

FLAGELLA
single; longer
wave-like motion = reverse bend-forward bend
recovery stroke: bend propagates up the flagellum
motion with several bends
Where cilia is found/used:
respi tract to remove mucus
uterus for propulsion of egg cell
attachment is called basal body
beat metachronically
smoke (cigarette) loosens cilia lining in lungs
(A) Trypsin-treated axoneme of sperm tail nexin linkers and
radial spokes cleaved ATP addition sliding of
microtubules axoneme is 7-8 times longer
(B) ATP-dependent movement of outer doublets restricted by
cross-linkage proteins in order for sliding to be converted
into bending of axoneme