Download Physiologic basis of EMG/NCS or what constitutes a waveform?

Nerve & Muscle Physiology
• Jeff Ericksen, MD
– VCU Health Systems PM&R
Topics *
• Relevant anatomy
• Cell functions for signal transmission
– Transport, resting potential, action
potential generation & propagation
– Neuromuscular transmission
– Muscle transduction
• Volume Conductor theory
Acknowledgements
• Electrodiagnostic Medicine by Daniel
Dumitru, MD
– Chapter 1: Nerve and Muscle Anatomy
and Physiology
• Superb text covering all aspects of
EMG/NCS
Cell membrane
• Necessary for life as we know it
• Border role for cell
– Separates intracellular from
extracellular milleau
• Allows ion and protein concentration
gradients to exist
– Creates electric charge gradients
Cell membrane
• Provides structure for cell
• Modulates cell interaction with
environment
– Mechanical, hormone-receptor
• Controls material flow into/out of cell
– Nutrition/waste management
3 Key Membrane Components
• Lipids 45-49%
– phospholipids, cholesterol & glycolipids =
amphipathic molecules
• Polar = hydrophilic vs. nonpolar = hydrophobic
• Proteins 45-49%
• Carbohydrates 2-10%
Lipid characteristics
• Membrane phospholipids have polar
head group with 2 nonpolar tails
• In water - nonpolar tail groups form
an inside excluding water
• 2 arrangements possible
– Micelle = tails inside, heads face out
– Bilayer
Lipid bilayer or fluid mosaic
model
• Phospholipid sheet with tails aligned
in center, heads facing out for a
head-tail-head sandwich
– No H2O at center, 75 Angstroms
• Model as 2-D liquid with 2 degrees of
freedom of motion for lipid
– Long axis rotation
– Lateral diffusion
Proteins in membrane
provide cell functions
• 2 membrane protein types
– Transmembrane = integral - across whole
layer, amphipathic
• Hydrophobic midportion acts with lipid layer
tails
• Hydrophilic section faces intra/extra
environment
– Peripheral proteins - inside or outside of
bilayer
Proteins
Membrane transport
• Lipid soluble molecules cross readily
but large water soluble molecules
need transport across bilayer
– Transport proteins - specific for ion or
molecule to cross
• Channel proteins - span bilayer, large center,
allow ion/molecule passage based on size
• Carrier proteins - binding with specific
material, conformational change then
crossing membrane
Membrane transport
• Diffusion
– Driven by kinetic
energy of random
motion
– Thru lipids or
proteins
– Follows
concentration
gradient
• Active transport
– Needs energy
source
– Fights
concentration or
energy gradient
Simple vs. Facilitated
diffusion
• Simple
– Crosses membrane
bilayer or channel
without binding
– Increases with
kinetic energy +
lipid solubility +
concentration
gradient
– Protein channels
specific for ions,
often gated by cell
functions
• Facilitated
– Transmemb
proteins
– Needs protein
binding,
conformational
change
– Speed of transport
limited by
conformational
change
Membrane transport
Carrier proteins
Channel protein
Simple diffusion
Diffusion
Facilitated
diffusion
Energy
Active transport
Active transport
• Acting on semi-permeable membrane
allows the cell to maintain a high
intracellular concentration vs.
extracellular fluid
• Requires active process as diffusion
would eventually equilibrate
concentrations across membrane
Active transport
• Transmembrane carrier protein uses
ATP energy to pump ions against
concentration gradient to develop
transmembrane resting potential
Resting membrane potential
• Excitable cells can generate and
conduct action potentials over
distances
• Intracellular space carries potential
difference of 60-90 mV, inside with
negative charge excess relative to
outside
Resting membrane potential
created by semi-permeable
membrane and ions
• Intracellular
– Na 50
– K 400
– Cl 52
• Extracellular
– 440
– 20
– 560
http://www.bioanim.com/Cell
TissueHumanBody6/O3chann
els/ionCloudPoints1ws.wrl
Nernst used thermodynamics in
1888 to determine work done
by membrane
• Work to move ion against
concentration gradient is opposite to
work to move against electrochemical
gradient
• Can calculate contributions from
different ions
– K = -75 mV, Na = +55 mV
Nomenclature
• Polarized membrane: Intracellular
potential is negative relative to
extracellular space
• Depolarization = less polarization of
the membrane -80mV -> +20mV
• Hyperpolarization = more polarization
of membrane -80mV -> -100mV
Na influx with K efflux
• Na driven by negative charge excess
inside + concentration gradient
• K driven by concentration gradient
• If continued, would lose resting
potential
Na - K ATP dependent pump
• Plasma membrane structure uses
active transport
• 2 K in for 3 Na out actively
• Thus 3 Na must diffuse in for 2 K out
Membrane potential from
Goldman-Hodgkin-Katz
equation
• Resting potential mostly from K
contributions
• If sudden Na permeability change,
potential approaches Nernst Na
potential rapidly
– Action potential!
Voltage dependent ion
channels
• Ion flow across through membrane
channels is initiated by membrane
potential changes
• If potential exceeds a threshold,
rapid increase in Na permeability
followed by later K permeability
increase
Voltage dependent ion
channels
• Extracellular Na activation gate with
intracellular inactivation gate and
slow K activation gait
• Conformational changes due to
membrane potential changes influence
ion permeability
Voltage gated channels
Channels and voltage
influence
• If resting potential depolarized by 15-20
mV, then activation gate opened with
5000x increase in Na permeability followed
by inactivation gate closure 1 msec later
• Slow K activation gate opens when Na
inactivation gate closes to restore charge
distribution, slight hyperpolarization
http://www.bioanim.com/Cell
TissueHumanBody6/O3chann
els/naChan1ws.wrl
Refractory periods
• Absolute = state when activation gait
cannot be reopened with a strong
depolarization current, the membrane
potential is relatively more positive
• Relative = state when activation gait
can be reopened by strong
depolarizing current as membrane
potential returns to equilibrium state
Action potential timing
Action potential propagation
• Na + charge influx spreads
longtiduinally down path of least
resistance to induce depolarization in
adjacent membrane, some
transmembrane spread
• As + charge builds up, attracts
intracellular - charges and they are
neutralized by new ICF + charges
AP propagation
• Less electrochemical hold of ECF +
charges which migrate and allow
depolarization of membrane further
• Process is repeated down axon until
end is reached
• AP is identical to AP from upstream
nerve area, all or none event
Nerve membrane modeling
• Capacitor = charge storage device,
separate poles separated by a
nonconducting material or dielectric
– Hydrophobic center to lipid bilayer is
good dielectric, allows membrane to
function well as a capacitor
Nerve membrane modeling
• Resistor = direct path to current flow
but with some impedance
• Nerve axon has both transmembrane
resistance as well as longitudinal
resistance
Current spread
• Membrane capacitor model suggests
transmembrane resistance is high,
hence current flows more
longitudinally vs. transmembrane
capacitance flow or ionic channel
resistance flow
Slow process
• Longitudinal AP spread requires
sequential depol. to threshold,
membrane capacitor discharge and
then alteration of proteins to turn on
Na activation channels. This process
can be slow.
• Hence unmyelinated nerve conducts
slowly = 10-15 m/sec.
Need velocity to interact
with environment!
•
longitudinal resistance will speed
– diameter will
resistance
• Eliminate need to fire all surrounding
tissue will velocity of conduction
– Insulate nerve to prevent leakage,
spread out the gated Na channels
• Myelin & Nodes of Ranvier
Myelin
• All peripheral nerve axons surrounded
by plasma membrane of a Schwann
cell
– Single layer of membrane = unmyelinated
nerve, multiple layers = myelinated nerve
– Gap between Schwann cell covers = node
of Ranvier
Myelinated axons
• Outer myelin sheath + axon plasma
membrane = axolemma covering
axoplasm
• Schwann cell membrane has lipid
sphingomyelin, highly insulating
• No Na channels under myelin, only at
nodes. K channels under myelin in
perinodal area
Current conduction with
myelin insulation
• AP at node, Na charge influx and
current spreads longitudinally down
axon
• Minimal leak between nodes, reduced
by 5000 vs. unmyelinated nerve
– Charge separation, reduced protein leak
channels & increased membrane
resistance account for this
Current conduction
• Circuit is closed by efflux of ionic current
at node
• Na ions accumulate beneath node, reduces
electrochemical pull on ECF Na above node,
they migrate back to upstream node to
close loop
• Above tends to increase + charge inside
membrane or depolarize to give AP
AP generation at node
• Nodes contain high # Na
channels which open with
depolarization
– Na influx starts process again
Myelin effects
• Conduction velocity increases
• Current and action potential jumps
from node to node = saltatory
conduction
• Optimal internodal length is 100x
axon diameter
• Optimal myelin/axon ratio is 60/40
Neuromuscular junction,
transducing the electrical signal
to mechanical force
Multiple branches from large
motor axons
What happens if varying
myelin and diameter in
branches?
NMJ anatomy
• Presynaptic
– Terminal axon
sprout
• Mitochodria
• Synaptic vesicles =
ACH
– Presynaptic
membrane
• Postsynaptic
– Motor endplate
•
•
•
•
•
Single muscle fiber
Mitochondria
Ribosomes
Pinocytotic vesicles
Postsynaptic
membrane
– ACH receptors
NMJ Electrochemical
conduction
• Considerable slowing in smaller diam
less myelinated branches
• AP depolarizes terminal axon, Na
conductance increases
– Calcium conductance also dramatically
increased
– Influx Ca++ in terminal axon
• Possibly facilitates fusion of ACH vesicles
with presynaptic membrane
Electrochemical
conduction….
• Vesicular fusion with presynaptic
membrane
• Open to synaptic cleft, release quantum of
ACH
– 100 vesicles per AP in mammals, 10k ACH per
vesicle
• Ca++ stays in terminal axon 200 ms, keeps
axon readily excitable for repeat
stimulation
ACH release
• Rapid diffusion across cleft in .5
msec timing, bind receptors
– Large transmembrane proteins with ACH
site and ion channel
– Ligand activated vs. voltage activated
• ACH binding induces conformational
change in ion channel
– 1 ms opening of cation specific channel =
Na, K, Ca, repels anions with charge
Postsynaptic ion channel
opening with ACH binding
• Predominant influx is Na, K blocked by
electrochem gradient, Ca concentration
gradient not that large
• Na influx locally depolarizes muscle
membrane= endplate potential reversal
which is not propagated = EPP
– Single packet of ACH from vesicle gives
MEPP
Muscle action potential
• Generated if sufficient ACH released
to cause postsynaptic membrane to
reach threshold, muscle membrane
depolarized and propagated impulse
follows
• Muscle AP travels along muscle
membrane = sarcolemma
– Similar to nerve, increased Na
permeability in + feedback loop
T-tubules
• Small volume favors K accumulation
during repolarization after AP, tends
to make membrane easy to depolarize
again
• Penetrate into muscle to spread AP
into fiber
• High surface area of T-tubules
increases capacitance qualities and
slows conduction in muscle
Excitation-Contraction
• AP in T-tubule induces Ca++ release in
SR terminal cisternae, exposure for
1/30 sec, then reuptake via pump
• Ca++ bind to troponin C, induces
conformational change of troponin
complex and influences tropomyosin
to actin relationship - mechanical
force
The End!