BIO 122 LECTURE 3: NEUROMUSCULAR PHYSIOLOGY

I.
SIGNALLING IN NERVES
II.
III.
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)
IV.
V.
Why action potential jump down axon
VI.
1. As charge spreads down an axon, myelination (Schwann
cells) prevents ion from leaking out the PM.
2. Charge spreads unimpeded until it reaches an unmyelinated
section of the axon (node of Ranvier, which is packed with
Na+ channels)
3. Electrical signals continue to jump down the axon much
faster than down an unmyelinated cell.
VII.
VIII.
Normal conduction of myelinated fibers high
density voltage-gated Na+ channel at node; saltatory
conduction of signal
IX.
Demyelination of nerve fibers in MS increased
Na+ channels along demyelinated axons (multiple
sclerosis)
X.
XI.
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
XII.
1. 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
2. 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
XIII.
XIV.
XV.

J4R4FFE

XVI.
XVII.
XVIII.
XIX.

Synaptic Transmitter at Neuromuscular Junction

(NMJ):
Acetylcholine Synthetic and Storage

XX.
XXI.
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
XXII.
XXIII. 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
XXIV.
1. Presynaptic Potential AP arriving at the terminal end of
an axon
2. 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
XXV.
XXVI. Multiple excitatory and inhibitory inputs onto
dendrites and the soma SUMMATE EPSP +
IPSP.
XXVII.
XXVIII. Spatial Summation
XXX.
several neurons
XXXII. stimulating at the same time
XXXIV. occurs at different sites of membrane
XXXVI.
XXXVII.
XXXVIII.
XXXIX.
XL.
XLI.

XLII.
XLIII.
XLIV.
XLV.
XLVI. 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)
LIII.

LIV.
LV.
LVI.
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
LVII.
LVIII. 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)
LIX.

current spreads bc fluid (without generation of AP)

dendrites summate the excitatory and inhibitory potentials
XLVII.
XLVIII.
XLIX.
L.
Termination of Synaptic Transmission
resorption (active reuptake) of neurotransmitter or its
breakdown products
enzymatic degradation of neurotransmitter (e.g.
Acetylcholinesterase)
LI.
LII.
Pre and Postsynaptic Inhibitions

LX.

LXI.
LXII.
LXIII.
b.

LXIV.

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

LXV.

LXVI.
LXVII. SENSORY RECEPTION
LXVIII.
LXIX. Receptor Cell
specialized cell responsive to internal and external stimuli
has the ability to convert energy into neural signal
LXX.
LXXI. stimulus receptor afferent nerve CNS
LXXII.
LXXIII.
LXXIV.
LXXV. 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+
LXXVI.
LXXVII. Characteristics:
LXXVIII.
1. An adequate stimulus elicits a graded RP, the amplitude of
which is a function of stimulus intensity
LXXIX.
LXXX. Adequate stimulus form of stimulus energy to
which the receptor is most sensitive or to where it normally
responds
LXXXI.
2. The frequency of resultant AP in a receptor is a coded
representation of the intensity of the adequate stimulus
LXXXII.
LXXXIII.
Receptor potential is graded and non-propagated.
LXXXIV.Action potential is non-graded and propagated.
LXXXV.

LXXXVI.

LXXXVII.
LXXXVIII. Sensory Transduction:
LXXXIX.
absorption of stimulus energy (SE)
transduction of SE to electrical signal amplification
of energy integration and conduction
XC.
XCI.
Sensory Reception and Processing:
XCII.
stimulus sense organ (accessory structure)
transducer (sensory cells) action potential (nerve
transmission) decoder (CNS)
XCIII.
XCIV. TRANSDUCTION: Excitation of Receptors to
Generate RP
XCV.
XCVI. Altered permeability of membrane to ions:
1. mechanical deformation of receptors
2. chemical application
3. temperature change
4. effects of electromagnetic radiation
XCVII.
XCVIII. Receptor Adaptation
decrease in the response of a receptor to a steadily
maintained stimulus over time
decrease in firing of AP despite maintained depolarization
XCIX.
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
C.
Adaptation Curves (Examples)
CI.

CII.

CIII.
1. 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
2. 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
3. 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
4. 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
5. 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)
CIV.

CV.
Dark State
cGMP-gated Na+ channels, which are open in the
dark
CIX.
membrane less negative
CXI.
active transport of Na+
CXIII. membrane more negative
CXV.
RMP = -40 mV normal in dark conditions
CXVII. MOVEMENT AND LOCOMOTION
CXVIII.
A. SKELETAL MUSCLES
CXIX.
CXX.
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
CXXI.
CXXII. 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)
CXXIII.
CXXIV. 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
CXXV.
CXXVI. Sarcomere
Z-M-Z
Z line -actinin/titin binds actin of adjacent sarcomeres
M line Mittel of sacromere
CXXVII.
CXXVIII.
Myosin
composed of two coiled polypeptide chains
tails are oriented towards the center of the sarcomere (M
line)
CXXIX.
CXXX. Actin
composed of two coiled actin molecules + regulatory
proteins

TROPOMYOSIN = covers actin binding sites

TROPONIN = theww binding sites (for

tropomyosin, actin and Ca2+ ions)
CXXXI.
CXXXII.EXCITATION
CXXXIII.
CXXXIV.
CVII.

CXXXV.
CXXXVI.
CXXXVII.

NMJ: Chemical Synapse Ach

CVIII.
CX.
CXII.
CXIV.
CXVI.

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

CXXXIX.
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)
CXL.
CXLI. Drugs that block transmission at NMJ
prevent impulse transmission
curariform drugs
CXLII.
CXLIII. Myasthenia gravis
autoimmune disease where antibodies attack, block or alter
the Ach receptors at NMJ prevents muscle contraction
mostly affect voluntary muscles
muscle weakness
CXLIV.
CXLV. How is Ca2+ released from sarcoplasmic reticulum?
CXLVI.
1. Plunger Model
ryanodine receptors block Ca2+ channels
AP: calcium lifts the ryanodine
CXLVII.
CXLVIII.

CXLIX.
2. Enzyme- or messenger-mediated mechanism
CL.
CLI.

CLII.

CLXIII.

CLIII.
CLIV.
CLV.
CONTRACTION
CLVI.
CLVII. Sliding Filament Mechanism
decreases in width: sarcomere, I band, H zone
no change: A band, myosin and actin filaments
CLVIII.
CLIX.

CLX.
CLXI.
CLXII.

Cross-Bridge Cycle

CLXIV.
CLXV.
CLXVI. Energy Sources for Contraction
CLXVII.
CLXVIII.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
CLXIX.
CLXX.
CLXXI.
CLXXII.
CLXXIII.
CLXXIV.
RELAXATION
CLXXV.
CLXXVI.
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)
CLXXVII.
CLXXVIII. Isotonic Contractions
CLXXX. muscle shortens with constant tension
CLXXXII.
CLXXXIV.

load < tension

CLXXXV.
Slow Muscle Fibers
CLXXXVII. slow but prolonged response
CLXXXIX. slow contraction, longer duration
CXCI. associated with smaller fibers innervated by smaller
nerves
CXCIII. extensive blood supply and mitochondria
CXCV. high myoglobin red/dark muscles
CXCVII. low levels of myosin ATPase and glycolytic enzymes

CXCIX. Type I/Slow Oxidative = depends on aerobic processes

CCXXII.

CCIII.
CCIV.
CCV.
B. SMOOTH MUSCLES
CCVI.
CCVII. Smooth Muscle Structure
CCVIII.
CCIX.

no striations
no sarcomere
no troponin
no T-tubules
less developed SR
CCX.
CCXI. Smooth Muscle Innervation: Autonomic
no NMJ
neurotransmitters are released from varicosites
CCXII.
CCXIII. Types:
1. Multi-unit
one nerve per muscle cell neurogenic
e.g. muscles found in iris of eyes, trachea, arteries
2. Single-unit
one nerve + gap junctions myogenic
e.g. peristaltic wave in GI tract
CCXIV.
CCXV. Smooth Muscle Contraction
CCXVI.
1. With excitation-contraction coupling
through neural input (autonomic nervous system)

Parasympathetic: Ach as NT binding with

muscarinic receptor

Sympathetic: NE as NT
2. Without E-C coupling
through hormones, paracrine agents (effects/signals
neighboring cells), etc. involving secondary messengers
CCXVII.
CCXVIII.
C. CARDIAC MUSCLES
CCXIX.
CCXX. Cardiac Muscle Structure
CCXXI.

CCXXIII.
with striation
with troponin
with developed SR
with T-tubules
CCXXIV.
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)
CCXXV.
CCXXVI.
CCXXVII.
CCXXVIII.
CCXXIX.
CCXXX.
CCXXXI.
CCXXXII.
CCXXXIII.
CCXXXIV.
CCXXXV.
CCXXXVI.
CCXXXVII.
CCXXXVIII.
CCXXXIX. Action Potential in Cardiac Myocyte
CCXL.
CCXLI.

CCXLII.
CCXLIII.Dyhydropyrinidine receptors are unable to affect
function of ryanodine receptors,

CCXLIV.
CCXLV.

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

RyRs.
CCXLVII.
CCXLVIII. Smooth
CCXLIX.
Cardiac
CCL.
CCLI. excitation: requires
both extra and
intracellular sources
of Ca2+
CCLII. contraction:
CCLIV. contraction:
Ca2+ binds with
mechanism is
calmodulin (vs.
similar to skeletal
skeletal =
but more calcium is
troponin)
released for AP
CCLIII. contracts more
generation more
slowly and
actin-myosin
exhibit more
interaction = to
prolonged
avoid tetany of
contraction with
heart
less ATP
CCLV. relaxation:
CCLVI. relaxation:
requires myosin
1. active transport of Ca2+
phosphatase
back into SR during
enzyme to
relaxation
dephosphorylat
2. 3 Na : 1 Ca antiport in
e myosin
SR and sarcolemmal
pump
CCLVII. sources of Ca2+
CCLVIII.
are both
extracellular
and intracellular
(SR)
CCLIX. extracellular
Ca2+ allows
prolonged
contraction
CCLXI. intracellular
increase in Ca2+
= due to nerve
stimulation or
hormonal/local
factors
CCLXIII.Thick Filament Regulation (Phosphorylation of
Myosin):
CCLXIV.
CCLXV. calmodulin + Ca2+ activates myosin light-chain
kinase (MLK) adds phosphate to myosin

phosphorylated myosin binds to actin

contraction
CCLXVI.
CCLXVII.
[vs. skeletal = Thin Filament Regulation]
depends on the uncovering of the thin filament (actin)
CCLXVIII.
CCLXIX.
D. NON-MUSCLE CELLS
CCLXX.
CCLXXI.
Cytoskeleton
network of protein filaments in eukaryotic cell cytoplasm
that provides shape, support and movement
cytomuslculature
CCLXXII.
CCLXXIII. 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
CCLXXIV.
CCLXXV.
Actin Filaments in Crawling Cells (Amoeboid)
CCLXXVI.
1. Trailing edge
where most actin is heavily distributed
2. Leading edge
pulls the cell forward
3. 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
CCLXXVII.

CCLXXVIII.
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
CCLXXIX. Growth cone
developing axon (terminal portion) not yet synaptically
connected

guides the axon in looking for synaptic target

lamellipodium + filopodium + microfilaments
CCLXXX.
CCLXXXI. Addition of G-actin to F-actin
filopodium
CCLXXXII.
CCLXXXIII. 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
CCLXXXIV.
CCLXXXV. Actin-binding Proteins: -actin, Filamin,
Fimbrin
determine the form + function of actin filaments

-actin = contractile bundles

filamin = gel

fimbrin = parallel bundles

CCLXXXVI.
CCLXXXVII. Steps in Cell Crawling
CCLXXXVIII.
1. Protrusion
of the leading edge
polymerization of actin subunits to form actin fils
2. Adhesion
to certain substrates
mostly stress fibers contribute to adhesion
cortex, hindi humahaba pero nagmo-move
*Deadhesion trailing end
3. Traction
interaction of actin-myosin
CCLXXXIX.
CCXC.

CCXCI.
CCXCII.
CCXCIII.
CCXCIV.
CCXCV.
CCXCVI.
CCXCVII.
CCXCVIII.
CCXCIX.
CCC.
CCCI.
CCCII.
CCCIII.
CCCIV.

CCCV.

Cytoplasmic Gel-Sol Conversion: Role in

Locomotion

CCCVI.
CCCVII.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
CCCVIII.
CCCIX.

CCCX.
CCCXI.

CCCXII.
CCCXIII.
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
CCCXIV.
CCCXV. FLAGELLA
single; longer
wave-like motion = reverse bend-forward bend
recovery stroke: bend propagates up the flagellum
motion with several bends
CCCXVI.
CCCXVII.
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
CCCXVIII.
CCCXIX.
CCCXX.
CCCXXI.

CCCXXII.
CCCXXIII.
CCCXXIV.
CCCXXV.
CCCXXVI. 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
CCCXXVII.
CCCXXVIII.

CCCXXIX.
CCCXXX.
In a cilium/flagellum, two adjacent doublets
cannot slide far because they are physically restrained
by proteins so they bend.
CCCXXXI.
CCCXXXII.

CCCXXXIII.
(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