[box type=”download”] Membrane potentials as being a property of all cell membranes Resting membrane potentials as a consequence of asymmetric distributions of Na and K Note: detail of the specific ionic and voltage changes is NOT required Action potentials as being a property of excitable tissues [/box]
A potential difference across the membrane – membrane potential, Em
In excitable tissues, resting Em is usually between –60 and –90 mV.
The cell contains negatively charged molecules (e.g. proteins) which cannot cross the membrane.
This fixed negative charge attracts K+, leading to accumulation inside the cell but the K+ concentration gradient drives K+ back out of the cell.
The cell therefore remains negatively charged compared to the outside, causing a potential difference across the membrane. Equilibrium is reached when the electrical forces exactly balance those due to concentration differences (Gibbs–Donnan equilibrium).
K+ Equilibrium potential, (EK) can be calculated from the Nernst equation.
Eg: intracellular [K+] = 120mmol/L and extracellular [K+] = 4 mmol/L, EK = ∼–90 mV. Intracellular [Na+] 10mmol/L and extracellular [Na+] 140 mmol/L, the ENa = +70 mV.
The ratio of permeability to K+ (PK) to Na+ (PNa) ranges between 25:1 and 100:1 in nerve, skeletal and cardiac muscle cells.
As a result EM in such cells at rest (resting membrane potential) is close to EK (–60 to –85 mV) and the electrochemical gradient for K+ is small.
Em does not equal EK because there is permeability to other ions, notably Na+.
As ENa is much more positive than Em, the Na+ electrochemical gradient is strongly inwards, forcing Na+ into the cell.
However, as PNa is relatively low, only a small amount of Na+ can leak in, though this is sufficient to slightly depolarize the membrane from EK.
A consequence of the above is that if PNa were suddenly increased to more than PK, then Em would shift towards ENa.
This is exactly what happens during an action potential, when Na+ channels open so that PNa becomes 10-fold greater than PK, and the membrane depolarizes.
[box type=”download”] Appreciation of the ionic basis of the action potential Depolarisation Importance of the threshold potential in initiating propagation Propagation based upon the all-or-nothing principle Repolarisation Ionic basis of the absolute and relative refractory periods[/box]
The action potential
Action potentials are initiated in nerve and skeletal muscle by activation of ligand-gated Na+ channels by neurotransmitters.
This increases PNa and causes EM to move towards ENa (i.e. become positive).
If the stimulus is sufficiently strong, Em depolarizes enough to reach the threshold potential (∼−55 mV), at which point voltage-gated Na+ channels activate, causing further depolarization, leading to a large transient increase in PNa so it is 10-fold greater than PK. As a result, Em rapidly approaches ENa (∼+65 mV), causing the sharp positive ‘spike’ of the action potential, which lasts about 1 ms in nerve and skeletal muscle.
The spike is transient because as Em becomes positive, the voltage-gated Na+ channels inactivate and PNa plummets, whereas a type of voltage-gated K+ channel (delayed rectifier) activates.
Thus PK is again much larger than PNa and Em returns towards EK (repolarization).
Delayed closure of the delayed rectifier K+ channels means that the PK:PNa ratio remains transiently greater than normal after repolarization, causing a transient hyperpolarization (excess negativity).
Following depolarization the Na+ channels remain inactive for about 1 ms until the cell is largely repolarized and, during this period, they cannot be opened by any amount of depolarization. This is known as the absolute refractory period during which it is impossible to generate another action potential.
For the following 2–3 ms, the transient hyperpolarization renders the cell more difficult to depolarize, an interval known as the relative refractory period, when an action potential can be generated only in response to a larger than normal stimulus.
Once initiated, an action potential can travel only in one direction with same amplitude (it is all-or-nothing).
The action potential is not due to changes in ionic concentrations, but to changes in ionic permeability.
Conduction of the generated action potential
[box type=”download”] Saltatory conduction as a product of myelination spaced by nodes of Ranvier Importance of myelination in terms of speed and energy efficiency Relation between nerve size and conduction speed Note: knowledge of the classification of nerve fibres (A, B, I, II etc) is NOT required[/box]
Depolarization moves along each segment of an unmyelinated nerve until it reaches the end. It is all-or-nothing and does not decrease in size.
Myelin is an insulator and the only areas of the myelinated axon that can be depolarized are those that are devoid of any myelin, i.e. at the nodes of Ranvier. The depolarization jumps from one node to another and is called saltatory, from the Latin saltare (to jump).
Saltatory conduction is rapid and can be up to 50 times faster than in the fastest unmyelinated fibres.
It also conserves energy by depolarizing only the nodes (not the whole length of the nerve fibre, as in unmyelinated fibres with up to 100 times less movement of ions).
All nerve fibres are capable of conducting impulses in either direction if stimulated in the middle of their axon; however, normally they conduct impulses in one direction only (orthodromically), from either the receptor to the axon terminal or from the synaptic junction to the axon terminal. Antidromic conduction does not normally occur.
Fibre diameters and conduction velocities
Nerve fibres range from 0.5 to 20 μm in diameter, with the smallest diameter unmyelinated fibres being the slowest conducting and the largest myelinated fibres the fastest conducting.