ELECTROPHYSIOLOGY

Prof. Yasmeiny Yazir

BAGIAN FISIOLOGI FK USU

 Plasma Membrane
Membrane potential = electrical voltage difference
across plasma membrane of cell
• caused by differences in ion concentrations
maintained by plasma membrane proteins
Membrane structure
• phospholipids
• integral proteins - form channels
 Membrane Channels
Two major classes of channels:
1. Leakage channels (non-gated or passive channels)
° always open
° more K+ than Na+ channels
- allow influx of Na+, efflux of K+
° found in cell body and dendrites
2. Gated channels
° open/close based on environment
° found in cell body, dendrites, axon hillock,
unmyelinated axons and myelinated axons
(nodes of Ranvier)
 Types of Gated Channels
• chemically gated* -- respond
to neurotransmitters,
hormones, ions (e.g,. H+, Ca2+)
° found in cell bodies and
dendrites
• voltage gated* -- respond to
change in membrane potential
° found in axon hillock, axon
• mechanically gated -- respond
to mechanical change
(vibration, pressure, stretch;
e.g., stretch or touch receptors)
 Resting Membrane Potential (RMP)
Intracellular environment different from extracellular
environment in ionic composition

Outside: Inside:
more Na+, Cl- more K+, protein (anion)

Negative inside compared to outside; RMP = -70 mV

 Resting Membrane Potential (RMP)
• cell membrane with a potential (difference in voltage
across membrane) is polarized
• in neuron, at rest:
° inside: more K+, protein (anion)
- K+ diffuses out of cell through open K+/ Na+
channels
° outside: more Na+, Cl-
- Na+ diffuses into cell through open K+/ Na+
channels
° ion gradients (necessary for passive moment of
ions) maintained by Na+/K+ pump (active transport
system)
 Sodium-Potassium (Na+/K+) Pump
Active transport
(requires ATP)
• uses transport
protein in Diffusion

membrane Diffusion

(Na+/K+ Pump)
• moves 3 Na+ out
of cell; 2 K+ into
cell
• sets up and maintains ion gradients necessary for
diffusion
 Types of Potentials
Graded Potential
• magnitude varies with stimulus
° more depolarization with stronger stimulus
° decays away from point of stimulus
Action Potential
• magnitude stays the same
• once started, passes along axon as nerve impulse
 Graded Potential
• magnitude varies with stimulus --> allows graded
responses
• localized
• short-lived
• membrane may be:
° hyperpolarized (more negative than resting
potential; caused by influx of Cl- efflux of K+), or
° depolarized (less negative than resting; caused by
influx of Na+)
• at receptor = receptor potential
• at synapse = synaptic potential
Depolarization and Hyperpolarization
 Graded Potential
• depolarization starts at area
of stimulus
• spreads by ions moving on
either side of membrane (not
from outside to inside)
• larger stimulus opens more
channels
• if membrane reaches
threshold (~ -50 to -55 mV),
action potential (AP) will be
initiated
 Action Potential
• membrane potential goes from -70 mV to +30 mV
then back to -70 mV (after hyperpolarization)
• all-or-none principle:
° either start and pass AP, or don’t
° continues once started
• passed through membrane of excitable cells
(neurons and muscles)
° called nerve impulse when passed through axon
 Action Potential (con’t)
• long-distance communication
• propagation is unidirectional (one direction away
from point of stimulation)
• includes depolarization, repolarization and
undershoot (hyperpolarization)
° depolarization: -70 mV to +30 mV
- based on influx of Na+
° repolarization: +30 mV to -70 mV
- based on efflux of K+
° undershoot (hyperpolarization): -70 mV to -90mV
- potassium permeability continues
Events of an Action Potential
 AP: Depolarization
stimulus

chemically-gated Na+ channels open

Na+ influx

graded depolarization of dendrite or cell body

spreads to axon hillock, if threshold reached  voltage-

gated Na+ channels open (#2 in figure)

Na+ influx (positive feedback)

timed gates on Na+ channels close, K+

channels open for repolarization
 AP: Repolarization
Na+ channels closed, gated K+ channels open

K+ leaves cell taking + charge with it  repolarization (#3)

goes past normal resting potential (hyperpolarization)

(#4)

gated K+ channels close

Na+/K+ pump returns Na+/K+ levels to resting

 AP: Refractory Period
Time during which neuron
membrane does not
respond normally to
additional stimuli
• Absolute refractory
period: time in which a
new AP cannot be
started
• Relative refractory
period: time in which
new AP can only be
started by stronger
stimulus
 Comparison of Graded and
Action Potentials
Characteristic Graded Potential Action Potential
Amplitude Variable Always the same (all-or-none)
Duration Variable (depends on Rapid membrane change
stimulus)
Channels Chemically- or Voltage-gated
mechanically-gated
Location Dendrites, perikaryon Axon hillock, axon
Propagation Localized (short-distance) Transmitted along axon as
impulse
Refractory period None (allows summation) Absolute (no new APs);
Refractory (only with stronger
stimulus)
Membrane voltage Depolarization or Depolarization, followed by
change hyperpolarization repolarization and
hyperpolarization
 Impulse Conduction
• action potential (AP) passed through the axon as
an impulse
• “Rapid, transient, self-propagating reversal in
membrane potential”
Raven & Wood, 1976
• two types of conduction:
° continuous
° saltatory
 Continuous Impulse Conduction
• involves passage of AP
along entire membrane
• occurs in unmyelinated
axons and muscle fibers
• depolarization/
repolarization occurs in
step-wise manner as
Na+ and K+ channels
open and close in
adjacent parts of
membrane
direction is one-way due to absolute refractory period
shown in light blue
 Saltatory Conduction
• AP passed from one node of Ranvier to the next
• occurs in myelinated fibers
• saves ATP (Na+/K+ pump only used at nodes)
• faster
 Stimulus Intensity
• affects number of impulses sent per unit time
• does not affect velocity of conduction
• also affects number of neurons involved
 Factors Influencing Impulse
Conduction: Intrinsic Factors
1. Fiber diameter
° larger (thicker) is faster (because of lower
resistance)
2. Degree of myelination
° myelinated fibers are quicker because of
saltatory conduction
° multiple sclerosis – degenerative autoimmune
disease in which myelin sheaths of CNS are
destroyed by person’s own antibodies
 Factors Influencing Impulse
Conduction: Intrinsic Factors

3. Three groups of fibers:

° A
° B
° C
• Groups based on:
° diameter
° degree of myelination
 Fiber Types - Group A
• Group A (fastest):
° largest diameter (thickest)
° thick myelin sheath
° conduction velocities of 15-150 m/s
° include somatic motor and some somatic
sensory (from skin, skeletal muscles and joints
- touch, pressure, hot/cold, stretch, tension)
 Fiber Types - Group B & C
• Group B (intermediate):
° intermediate diameter
° thin myelin sheath
° conduction velocities of 3-15 m/s
• Group C (slowest):
° small diameter
° no myelin sheath (continuous conduction)
° conduction velocities of 1 m/s, or less
• Group B & C include:
° autonomic NS motor fibers to viscera
° sensory fibers from viscera
° small somatic fibers from skin (pain, some
pressure and light touch receptors)
 Factors Influencing Speed of
Conduction: Extrinsic Factors
Factors other than axon itself
1. temperature – due to general influence of heat on
chemical reactions
° warmer goes faster
° colder goes slower
2. pH
° decreased pH < 7.35 (increased H+) 
decreased excitability (depression)
° increased pH > 7.45 (decreased H+) 
increased excitability
 Extrinsic Factors (con’t)
3. excessive or prolonged pressure (interrupts blood flow)
4. inhibitory chemicals reduce membrane permeability to
Na+ (harder to depolarize)
° alcohol, sedatives, anesthetics
5. excitatory chemicals cause easier depolarization
° caffeine, nicotine
6. Ca2+ levels
° low Ca2+ - increases excitability
° high Ca2+ -decreases excitability
 Synapses
• junctions between neurons at which information is
passed from one neuron (presynaptic neuron) to
another (postsynaptic neuron)
• junction between neuron and effector (muscle or
gland) usually called neuroeffector junction (NEJ)
° neuromuscular junction (NMJ)
- neuron to muscle
° neuroglandular junction (NGJ)
- neuron to gland
 Structure of Distal End of Axon

• telodendria – terminal branches of axon

° allow axon to contact more than one cell or one
cell in several places
• axonal terminals = synaptic end bulbs
° contain neurotransmitter (or gap junctions)
• synaptic cleft – space between presynaptic and
postsynaptic membranes
 Types of Synapses
Defined by:
1. location: where signal comes from (e.g., axon) to
where it goes (e.g., dendrite, muscle)
2. how signal is transferred
a. based on location:
° neuron-neuron
° neuron-muscle
° neuron-gland
b. based on method of information transfer:
° electrical synapses
° chemical synapses
 Synapse Locations
Based on locations, most common are:
• axodentritic = axon (presynaptic) to dendrite
(postsynaptic)
• axosomatic = axon (presynaptic) to cell body, or
soma (postsynaptic)
• axoaxonic = axon (presynaptic) to axon or axon
hillock (less common than the other 2)
 Electrical Synapses
• less common type of synapse
• joined by gap junctions
• cells said to be “electrically coupled”
• very rapid transmission
• excitatory only
• allow bi-directional flow
• importance:
° allow synchronization of neuronal firing (important
to stereotypical behavior)
° important during development of nervous system
(later, most replaced by chemical synapses)
• also present in visceral smooth muscle, cardiac muscle
Chemical Synapses
• axonal terminal of presynaptic
neuron releases neurotransmitter
(NT) from synaptic vesicle into
synaptic cleft
• postsynaptic membrane (of
neuron or effector) contains
receptors that recognize NT
• slower than electrical
• unidirectional (one way)
• inhibitory or excitatory
• found at:
° most neuron-neuron
synapses
° neuroeffector junctions
 Events at Chemical Synapse
1. impulse within presynaptic neuron reaches axon
terminal, depolarizes membrane
 voltage-gated Na+ and Ca2+ channels open in
presynaptic membrane --> Ca2+ enters cell
2. entrance of Ca2+ into cell signals synaptic vesicles
to fuse with axonal plasma membrane
 for release of NT into synaptic cleft (exocytosis)
 Events at Chemical Synapse (con’t)
3. NT diffuses across synaptic cleft
4. NT binds to its specific receptor on postsynpatic
membrane
5. ion channels open in postsynpatic membrane
allowing ion movement
 Postsynaptic Potentials and
Synaptic Integration

• transmission from presynaptic to postsynaptic

neuron is excitatory or inhibitory depending on
type of NT released
° each presynaptic neuron releases either
excitatory NT or inhibitory NT
• postsynpatic membranes normally dendrite or cell
body (soma or perikaryon)
 Postsynaptic Potentials and
Synaptic Integration
• reaction of receptors to NTs is graded, response
depends on number of receptors involved (which
depends on amount of NT released)
° excitatory postsynaptic potentials (EPSPs)
° inhibitory postsynaptic potentials (IPSPs)
 Excitatory Synapses and EPSPs
• binding of NT released by presynaptic membrane to receptor (on
postsynaptic membrane) causes opening of membrane channels that
allow both Na+ and K+ to diffuse across postsynaptic membrane

• because more Na+ enters than K+ leaves

--> net depolarization
• local graded excitatory postsynaptic potential
(EPSP)
• if EPSP is sufficiently large, may spread to
axon hillock leading to AP
Excitatory Synapses and EPSPs
 Inhibitory Synapses and IPSPs
• binding of NT released by presynaptic membrane
to receptor (on postsynaptic membrane) causes
opening of membrane channels that allow K+ to
diffuse out of post-synaptic cell, or Cl- to diffuse
in, or both
• causes hyperpolarization
 Modification of Synaptic Events
Temporal summation
• 1 or more presynaptic neurons fire before 1st
EPSP fades
• if summed EPSP is large enough, then get AP
 Modification of Synaptic Events
Spatial summation
• large number of axonal terminals from different
neurons or the same neuron fire at the same time
• if EPSP is large enough, then get AP
 Spatial Summation EPSP and IPSP
• IPSP and EPSP have opposite effects
• if only IPSPs occur, postsynaptic membrane becomes
hyperpolarized
° effects of IPSP may be temporally or spatially
summed
• usually IPSPs prevent membrane from becoming as
depolarized as it would with only EPSPs
Synaptic Potentiation and Facilitation
• synaptic potentiation: presynaptic axonal
terminal that has received repeated (in short
period of time) or continuous stimulation
contains more intracellular Ca2+ than normal
triggers greater release of NT into synaptic cleft
--> produces larger EPSP in postsynaptic
cell
(important in memory and learning processes)
• facilitation: postsynaptic neuron that has been
partially depolarized is more likely to undergo
AP,
 Termination of NT Effects
1. removal from cleft by reuptake into astrocytes
or presynaptic membrane (e.g.,
norepinephrine)
2. degradation of NT by enzymes present in
postsynaptic membrane or synaptic cleft
• e.g., acetylcholine [ACh] degraded by the
enzyme acetylcholinesterase - [AChE]
3. diffusion away from cleft
 Functional Classification of
Neurotransmitters (NTs)
A. Based on effects
° excitatory – cause depolarization (glutamate)
° inhibitory – cause hyperpolarization (GABA)
° effect of some depends on postsynaptic
membrane receptors
- ACh and NE have different receptor types –
some that cause excitation and other types that
causes inhibition
B. Based on mechanism of action
° direct (channel-linked receptors)
° indirect (G protein-linked receptors = second
messenger system)
 Modes of Action: Direct Action
• excitatory examples:
aspartate, acetylcholine
(ACh), glutamate, ATP
*open Na+/K+, Ca2+
channels leading to
• open ion channels depolarization
• immediate and localized • inhibitory examples:
action gamma aminobutyric acid
• action depends on binding (GABA), glycine
of NT to receptors followed *open Cl- or K+ channels
by channel activation, ion leading to
influx and membrane hyperpolarization
potential changes
 Modes of Action: Indirect Action
• slower, longer-lasting effects
• work through second messengers
° binding of NT with receptor activates G protein
in membrane which works through cyclic AMP
(cAMP = second messenger) to:
- regulate ion channels (open or close)
- activate kinase enzymes within cytoplasm
(activate proteins in cytoplasm)
 Modes of Action: Indirect Action
Examples
• Biogenic amines (dopamine, norepinephrine, epinephrine)
• Peptides (endorphins, dynorphins, substance P)
• ACh (at muscarinic receptors)
 Structural Classes of
Neurotransmitters
• Classified according to chemical structure:
° Acetylcholine (ACh)
° Biogenic Amines
° Amino Acids
° Peptides
° Novel Messengers
 Acetylcholine (ACh)
• first NT to be discovered
• excitatory to skeletal muscles
• excitatory/inhibitory to viscera
• found in CNS and PNS (NMJ with skeletal muscle,
NEJ for parasympathetic nervous system)
• formed from acetyl-CoA and choline
• degraded by acetylcholinesterase (AChE)
• Myasthenia gravis - autoimmune disorder of skeletal
muscle ACh receptors
• Alzheimer’s disease - decreased ACh level in brain
that ultimately results in mental deterioration
 Biogenic Amines
• synthesized from amino acid tyrosine
• found in CNS and PNS
° catecholamines
- norepinephrine [NE], epinephrine, dopamine,
- excitatory or inhibitory
° indolamines
- seratonin and histamine
- generally inhibitory
• play role in emotional behavior and help regulate
biological clock; norepinephrine is main NT of
sympathetic division of ANS
• schizophrenia - overproduction of dopamine
• Parkinson’s disease - deficient dopamine in basal
ganglia
 Amino Acids & Peptides
• Amino Acids
° GABA = gamma amino butyric acid (principal
inhibitory NT in brain),
° glycine (generally inhibitory NT, in spinal cord),
° glutamate (CNS, excitatory)
• Peptides (Neuropeptides)
° strings of amino acids produced in CNS and PNS:
- endorphins and enkephalins (natural opiates)
- substance P (mediator of pain signals)
° some also produced by nonneural tissues (e.g.,
cells of GI tract - somatostatin, cholecystokinin,
vasoactive intestinal peptide [VIP])
 Novel Messengers
Neurotransmitters that don’t fit other categories
• NO = nitric oxide
° involved in long-term synaptic potentiation (learning and
memory)
° relaxation of intestinal smooth muscles
° responsible for brain damage in stroke patients
• ATP = adenosine triphosphate
° promotes synthesis and uptake of other NTs in CNS and
PNS
• CO = carbon monoxide
° enhances neurotransmission in some circuits involved in
logic
° regulator of cyclic GMP (second messenger)
 Organization of Neurons:
Types of Circuits
• Simple series circuit
• Converging circuit
• Diverging circuit
• Reverberating (oscillatory) circuit
• Parallel after-discharge circuit
 Simple Series Circuit
• one presynaptic neuron goes to one postsynaptic
neuron; e.g., simple reflex arc
presynaptic

synapses

postsynaptic
 Converging Circuits
• several presynaptic
axonal terminals go to
single postsynaptic
neuron (output)
• input from several
pathways produces
single result
• e.g., voluntary vs sub-
conscious breathing;
“happy baby”
 Diverging Circuits
• one presynaptic neuron --> several postsynaptic
neurons
• e.g., single motor neuron from brain may go to
several motor neurons in spinal cord (thence to
several muscle fibers)
e.g., single sensory neuron to CNS may be part of
reflex but also send info to brain
 Reverberating (Oscillatory) Circuits
• chain of neurons with synapses to neurons earlier
in circuit
° sleep-wake cycle
° breathing
° possibly short-term memory
° some motor activities (arm swinging)
 Parallel After-Discharge Circuit
• one presynaptic neuron fires to several
postsynaptic neurons arranged in parallel that
eventually result in common output
• many different responses occur simultaneously
° may be involved in problem solving