PSYCH 3BN3 Chapter Notes - Chapter 3: Tetraethylammonium, Tetrodotoxin
Chapter 3: Voltage-Dependent Membrane Permeability
Ionic Currents Across Nerve Cell Membranes
1. A transient increase in the permeability of the neuronal membrane to Na+ initiates
the action potential.
2. A key to understanding this phenomenon is the observation that action potentials
are initiated only when the neuronal membrane potential becomes more positive
than a threshold level.
1. This observation suggests that the mechanism responsible for the increase in
Na+ permeability is sensitive to the membrane potential.
3. The fact that the Na+ permeability that generates the membrane potential change
is itself sensitive to the membrane potential presents both conceptual and
practical obstacles to studying the mechanisms underlying the action potential.
1. A practical problem is the difficulty of systematically varying the membrane
potential to study the permeability change, because such changes in
membrane potential will produce an action potential, which causes further,
uncontrolled changes in the membrane potential.
4. Voltage clamp method: a technique that uses electronic feedback to
simultaneously control the membrane potential of a cell and measure the trans
membrane currents that result from the opening and closing of ion channels.
5. In the late 1940s, Alan Hodgkin and Andrew Huxley used the VC technique to
work out the permeability changes underlying the action potential.
1. They were the first investigators to test directly the hypothesis that potential-
sensitive Na+ and K+ permeability changes are both necessary and sufficient
for the production of action potentials.
1. The fact that membrane depolarization elicits these ionic currents
establishes that the membrane permeability of axons is indeed voltage-
Two Types of Voltage-Dependent Ionic Currents
6. The results demonstrate that the ionic permeability of neuronal membranes is
voltage-sensitive, but the experiments don’t identify how many types of
permeability exist, or which ions are involved.
7. The voltage sensitivity of the early current gives an important clue about the
nature of the ions carrying the current-namely no current flows when the
membrane potential is clamped at +52 mV.
1. For the squid neurons studied by Hodgkin and Huxley, the external Na+
concentration is 440 mM, and the internal Na+ concentration is 50 mM.
8. Removal of external Na+ has little effect on the outward current that flows after
the neuron has been kept at a depolarized membrane voltage for several
1. This further result shows that the late, outwards current must be due to the
flow of an ion other than Na+.
1. Several lines of evidence present Hodgkin, Huxley and others showed that
this outwards current is caused by K+ exiting neuron.
9. Taken together, these experiments show that changing the membrane potential to
a level more positive that the resting potential produces two effects: an early
influx of Na+ into the neuron, followed by a delayed efflux of K+.
1. The early influx of Na+ produces a transient inward current, whereas the
delayed efflux of K+ produces a sustained outward current.
1. The differences in the time course and ionic sensitivity of the two fluxes
suggest that two different ionic permeability mechanisms are activated by
changes in membrane potential.
2. The differential sensitivity of Na+ and K+ currents to these drugs provides
strong additional evidence that Na+ and K+ flow through independent
3. Tetrodotoxin, tetraethylammonium, and other drugs that interact with specific
types of ion channels have been extraordinarily useful tools in characterizing
these channel proteins.
Two Voltage-Dependent Membrane Conductances
10. Membrane conductance: the reciprocal of membrane resistance. Changes in
membrane conductance results from, and are used to describe, the opening or
closing of ion channels.
1. Closely related, although not identical to membrane permeability.
11. If membrane conductance (g) obeys Ohm’s Law (which states that voltage is
equal to the product of current and resistance), then the ionic current that flows
during an increase in membrane conductance is given by: Iion= gion (Vm-Em).
12. From these measurements, Hodgkin and Huxley were able to calculate gNa and gk,
from which they drew two fundamental conclusions.
1. The first conclusion is that the Na+ and K+ conductances change over time.
1. For example, both Na+ and K+ conductances require some time to
2. The second conclusion derived from Hodgkin and Huxley’s calculations is
that both the Na+ and K+ conductances are voltage-dependent- that is, both
conductances increase progressively as the neuron is depolarized.
13. The voltage clamper experiments carried out by Hodgkin and Huxley showed that
the ionic currents that flow when the neuronal membrane is depolarized are due
to three different voltage-sensitive processes:
1. Activation of Na+ conductance
2. Activation of K+ conductance
3. Inactivation of Na+ conductance.
Reconstruction of the Action Potential
14. Refractory period: the brief period after the generation of an action potential
during which a second action potential is difficult or impossible to elicit.
15. The Hodgkin and Huxley model also provided many insights into how action
potentials are generated. .
16. The coincidence of the initial increase in Na+ conductance with the rapid rising
phase of the action potential demonstrates that a selective increase in Na+
conductances is responsible from action potential initiation.
17. This mechanism of action potential generation represents a positive feedback
loop: activating the voltage-dependent Na+ conductances increases Na+ entry into
the neuron, which makes the membrane potential depolarize which lease to the
activation of still more Na+ conductance, more Na+ entry, and still further
18. The regenerative quality explains why action potentials exhibit all-or none
behaviour and why they have a threshold. The delayed activation of the K+
conductance represents a negative feedback loop that eventually restores the
membrane to its resting state.
Long-Distance Signalling By Means of Action Potentials
19. The mechanism of action potential propagation is easy to grasp once one
understands how action potentials are generated and how current passively flows
along an axon.
20. The opening of Na+ channels causes inward movement of Na+, and the resultant
depolarization of the membrane potential generates an action potential at that
1. Some of the local current generated by the action potential will then flow
passively down the axon, in the same way that sub threshold currents spread
along an axon.
21. The resulting refractoriness of the membrane region where an action potential
has been generated prevents subsequent re-excitation of this membrane as action
potentials from propagating backwards, toward their point of initiation, as they
travel along an axon.
Increased Conduction Velocity As A Result of Myelination
22. Conduction Velocity: the speed at which an action potential is propagated along
1. It is an important parameter because it defines the time required for electrical
information to travel from one end of a neuron to another and, thus, limit the
flow of information within the nervous system.
23. One way of improving passive current is to increase the diameter of an axon,
which effectively decreases the internal resistance to passive current flow, is to
increase the diameter of an axon.
1. The consequent increase in action potential conduction velocity presumably
explains why giant axons evolved in invertebrates such as squid, and why
rapidly conducting ones.
24. Myelination: process by which glial cells (oligodendrocytes or Schwann cells)
wrap around axons to form multiple layers of glial cell membrane, thus insulating
the axonal membrane and increasing conduction velocity.
25. Nodes of Ranvier: periodic gaps in the myelination of axons where action
potentials are generated.