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Electrical Signals in Neuron (1)
Dr.Kyaw Min
Associate Professor
Department of Biomedical Sciences & Therapeutics
School of Medicine
Universiti Malaysia Sabah
Introduction
• Human Central Nervous System contains about 100 billion neurons
• Neurons have evolved from primitive neuroeffector cells which respond to various stimuli by contracting.
• In more complex animals, muscle – contraction neurons – integration and transmission of nerve impulse
One of the characteristics of life is excitability – ability to response to a stimulus.
Stimulus Response:
any change: physicochemical
electrical disturbance at the
chemical cell membrane:
mechanical local or
thermal propagated
The excitable tissues (nerve& muscle) respond to stimuli by changing their membrane potential and this is called electrical response.
Excitability depends on
electrical properties of cell membrane:
Membrane potential
Membrane resistance
Membrane capacitance
Resting Membrane Potential (RMP)
Under resting or unstimulated condition, there exists an electrical potential difference across the cell membrane with the inside negative relative to the exterior.• Typically -70 mV (-40 to -90 mV)• membrane is said to be polarized• found in almost all cells
The decline in membrane potential (eg. from –70 mV to –60 mV) is called depolarization.
The return of the membrane potential towards its resting level (back to –70 mV) is called repolarization.
If there is an increase in membrane potential (eg.from –70 mV to –80 mV), it is called hyperpolarization.
Genesis of Membrane Potential
development of RMP depends upon:
- unequal distribution of ions across the cell
membrane
- nature of the membrane- selective permeability
Concentration of some ions inside and outside mammalian spinal motor neuron
Ion Concentration(mmole/L of H2O)
Inside the Outside the
cell cell
Equilibrium potential
(mV)
Na+
K+
Cl-
15.0 150.0
150.0 5.5
9.0 125.0
+60
-90
-70
Unequal distribution of ions across the cell membrane
-Na+-K+ pump maintains high intrcellular K+ concentration and high extracellular Na+ concentration
- Donnon effect- the presence of non-diffusible anion proteins and organic phosphates
Nature of the membrane with selective permeability
Cell membrane at rest is a hundred fold more permeable to K+ than it is to Na+ (via passive non-gated channels,ie., continually open = leakage channels)
Ion channels
• Leakage channels
• Voltage-gated channels
• Ligand-gated channels
• Mechanically gated channels
Na+
Na+
K+
K+
3Na+
2K+
A-
K+K+ K+
___
_ K+
+
++
+
Genesis of membrane potential
Genesis of membrane potential
• Concentration gradient for K+ facilitates its movement out of the cell via K+ channel
• Its electrical gradient is in the opposite(inward) direction
• Since membrane is impermeable to most of anions in the cell, K+ efflux is not accompanied by equal flux of anions.
Genesis of MP (continued)
At equilibrium,
- tendency of K+ to move out is balanced by its tendency to move into the cell
- there is a slight excess of cations on the outside and anions on the inside
- this equilibrium state is maintained by Na+-K+ pump which is also electrogenic (contributing about 3 mV)
Genesis of MP (continued)
• Na+ influx does not compensate the K+ efflux because cell membrane at rest is a hundred fold less permeable to Na+ than to K+.
Cl- tends to diffuse in along the concentration gradient. However, because equilibrium potential for Cl- being identical to the measured resting membrane potential(-70 mV), the gradients opposes Cl- influx .
Genesis of MP (continued)
The number of ions responsible for the membrane potential is a minute fraction of the total number present and the total concentration of positive and negative ions are equal everywhere except along the membrane.
Maintenance of Membrane Potential:
RMP K+ efflux , Cl- influx
RMP K+ influx , Cl- efflux
Membrane Resistance
The cell membrane has nonpolar lipid bilayer in the interior and therefore resists current flow across it. Thus current flows more freely along the polar outside and inside of the membrane than across it. This property forms for the basis for spatial summation
Membrane capacitance
The cell membrane can store electrical charges, acting as a capacitor.
• An electrical capacitor is defined as two conducting materials separated by an insulating material.
• For the cell, the conducting materials are the polar hydrophillic regions facing the ECF and ICF, the insulating material is nonpolar hydrophobic interior of fatty acid tails.
Membrane Capacitance (Contd.)
• Because the lipid bilayer is penetrated by ion channels, the membrane acts as a leaky capacitor.
• This property forms the basis of temporal summation.
Figure-2.2: a motor neuron
Axon telodendria
Synaptic knobs
Figure 2-3. Top: Relation of Schwann cells to axons in peripheral nerves. On the left is an unmyelinated axon, and on the right is a myelinated axon. Bottom: Myelination of axons in the central nervous system by oligodendrogliocytes. One oligodendrogliocyte sends processes to up to 40 axons.
Figure- 2.4: Functional components of a neuron
Distribution of ion channels in myelinated neurons
Na+ channels
Cell body - 50-70/um2
The initial segment - 350-500/um2
Nodes of Ranvier - 2000-12000/um2
Along the axon of unmyelinated neurons
– 110/um2
• In many myelinated neurons, the
Na+ channels are flanked by K+ channels
Excitation of Neurons
• Nerve cells have a low threshold for excitation.
• The stimulus may be electrical, chemical or mechanical.
Two types of physicochemical disturbances
1. Local, non-propagated potential Graded potentials
2. Propagated potentials,
Action potentials or nerve impulse
Graded Potentials
• Depolarizing Graded Potential
Membrane becomes less polarized :
inside less negative
• Hyperpolarizing Graded Potential
Membrane becomes more polarized :
inside more negative
Graded potentials
Examples:
• Local response
• Electrotonic potentials
• Postsynaptic potentials
• Receptor potentials or generator potentials
Figure-2.8: Electrotonic potentials
At cathode-
Catelectrotonic potential- localized depolarizing potential change that rises sharply and decays exponentially with time due to repolarizing forces (K+ efflux and Cl- influx )
up to about 7 mV of depolarization, size of response is proportionate to the magnitude of stimulus
At anode-Anelectrotonic potential- hyperpolarizing potential change of similar duration. With stronger stimuli, size of response remains proportionate to the magnitude of stimuli
Local response
At the cathode
With the stronger stimuli (producing depolarization 7-15 mV), responses are greater than expected from the magnitude of stimulus
- Due to active participation of the membrane- opening of the voltage-gated Na+ channels ( Hodgkin cycle)
Generation of Action potential
Fig-2.6. An action potential
Figure 2-7. Diagram of the complete action potential of a large mammalian myelinated fiber, drawn without time or voltage distortion to show the proportions of the components.
Firing level
At 15 mV of depolarization, depolarizing forces overwhelm the repolarizng processes
Runaway spike potential (action potential) results.
Measurement of electrical events
Electrical events are rapid- measured in milliseconds (mS)
Potential changes are small- measured in millivolts (mV)
Detailed study by using:
• microelectrodes (tip diameter less than 1um)
• Electronic amplifier (amplifying 1000 times or more)
• Cathode –Ray Oscilloscope (almost inertia-less with almost instantaneous responding “lever”)
All-or-none law
Subthreshold stimulus- no action potential
At or above threshold stimulus- a full-fledged action potential with a constant amplitude and form.
No increment or other change as long as other experimental conditions remain constant
This law applies to single unit preparation under constant experimental conditions.
Ionic basis of the action potential:
The spike potential
Conductance of an ion is the reciprocal of its electrical resistance in the membrane and is a measure of membrane permeability to that ion
Figure-2.12: conductance changes during action potential
Firing level at 15 mV of depolarization
• The membrane potential at which a runaway depolarization is initiated
• There is sudden decline of membrane potential due to the operation of regenerative positive feedback cycle (Hodgkin cycle)
Depolarization opening of voltage-gated Na+
channel (Na+ channel activation)
further
Na+ influx
Regenrative positive feedback Hodgkin cycle
The resulting Na+ influx is so great that it temporarily swamps the repolarizing forces, completely abolishing the membrane potential and even reversing it (inside positive about 35 mV)
Equilibrium potential for mammalian neurons is about 60 mV.
Membrane potential approaches this value but does not reach it, because,
1. Na+ channel opening is short-lived, rapidly entering a closed state (inactivated) and remains in this state for a few milliseconds.
2. Reversal of membrane polarity
The falling (repolarization) phase is due to:
1. cessation of increase in Na+ influx as a result of rapid closure of Na+ channel,
2. reversal of electrical gradient (inside positive) and
3. increased K+ efflux due to slower and more prolonged opening of voltage-gated K+ channels
Figure-5.7 (p57): Na+ and K+ channel activation and inactivation
Na+ channel
Activation- at -70 to -50 mV of membrane potential, activation gate opens, increasing Na+ permeability of the membrane as much as 500 to 5000 fold
Inactivation- The inactivation gate closes a few 10,000th of a second after activation gate opens. It will not reopen until membrane potential returns to RMP.
K+ channel
When membrane potential rises from -70 mV toward zero, K+ channel opens slowly. They mainly open just at the same time the Na+ channels begin to close.
After –depolarization
This may be due to decreased rate of K+ efflux as a result of build-up of K+ immediately outside the membrane.
After-hyperpolarization
This is due to continued increase in K+ efflux as a result of slow return of K+ channels to the closed state.
Change in excitability during action potential
Excitability changes during action potential Phase Excitability
•Period from the time firing - totally inexcitable
level is reached till repolarization
is one-third complete
(absolute refractory period)
•From that point, repolarization is - decreased excitability
one-third complete, to the start of
After-depolarization
(relative refractory period)
Change in excitability (continued)
Phase Excitabilty
After-depolarization - increased
After –hyperpolarization - decreased
Refractory period
• Absolute refractory period coincides with the period of Na+ channel activation and inactivation. Inactivated Na+ channels cannot reopen; they first must return to the resting state.
Refractory period
• Relative refractory period coincides with the period when voltage-gated K+ channels are still open after inactivated Na+ channels have returned to their resting state.
Refractory period
• Larger-diameter axons have a larger surface area and have a brief absolute refractory period of 0.4 msec. Because second nerve impulse can arise very quickly, up to 1000 impulses per second are possible.
• Small-diameter axons have absolute refractory periods as long as 4 msec. enabling them to transmit a maximum of 250 impulses per second.
Figure-2.10: Conduction of nerve impulse
current sink
circular current flows (local circuits)
electrotonic depolarization
Conduction of nerve impulse
An active, self propagating process
Impulse moves along the nerve axon at a constant amplitude and velocity by;
• circular current flow
• successive electrotonic depolarization to the firing level of the membrane ahead of the action potential
Saltatory conduction
Conduction in myelinated nerve has a similar pattern.
Myelin is an effective insulator. Current flow through it is negligible.
Depolarization jumps from one node of Ranvier to the next.
Current sink at the active node serves to electrotonically depolarize the node ahead.
Saltatory conduction (contd.)
• A rapid process- 50 times faster than the fastest unmyelinated fibres.
Orthodromic and antidromic conduction
An axon can conduct impulses in either direction.
Orthodromic conduction
In motor nerves, from initial segment to terminal button;
In sensory nerves, from first node of Ranvier to terminal button.
Antidromic conduction
Conduction in the opposite direction.
Conduction of nerve impulse in myelinated axon (Saltatory conduction)
Encoding of stimulus intensity
• Frequency of impulses
• number of sensory neurons recruited (activated)
Comparison of Graded Potentials and Action Potentials
Graded PotentialsOrigin:
Arise mainly in dendrites
and cell body(some arise
in axons)
Types of channels :
Ligand-gated or
mechanically gated ion
channels
Action Potentials
- Arise at trigger zones and propagate along the axon
- Voltage-gated channels for Na+ and K+
Graded Potentials
Conduction:
Not propagated, localized
Amplitude:
Depending on the
strength of stimulus
Action Potentials
- Self-propagating
- all-or-none
Graded Potentials
Duration:
Typically longer
ranging from several msec
to several min.
Polarity:
Depolarizing or
Hyperpolarizing
Action Potentials
- Shorter, ranging from 0.5 to 2 msec.
- Always consists of depolarizing phase followed by repolarizing phase and return to resting membrane potential
Graded Potentials
Refractory period:
Not present, thus spatial
and temporal summation
can occur
Action Potentials
- present
Nerve fibre types and functions
The greater the diameter of a given nerve fiber, the greater its speed of conduction.
Summary • Resting Membrane potential• Different types of ion channels• Excitation of neuron
- graded potential and action potential• Ionic basis of action potential• Excitability changes during action potential :
Refractory period• Conduction of nerve impulse• Comparison between graded potentials and action
potentials• Nerve fibre types and functions
