The Ionic Basis of Electrical Activity in Nerve and Muscle

SUMMARY Four methods of determining the potential difference across the surface membrane of living cells are described. In a wide range of excitable tissues the resting membrane potential is of the order of 50–100 mV. and the action potential of the order of 80–130 mV. At the height of activity the potential difference across the membrane is reversed by 30–50 mV. The potassium concentration inside most excitable cells is 20–50 times greater than that in the external medium; sodium is 3–15 times more concentrated outside than it is inside, while chloride is 5–50 times more concentrated outside than inside. Isolated fibres lose potassium and gain sodium and chloride ions. Potassium appears to exist as a free ion inside nerve and muscle fibres. The nature of the organic anions which balance the high concentration of potassium inside excitable cells is still largely unknown. In certain cases amino‐acids such as aspartic acid are present in high concentrations. The resting membrane behaves as though it were moderately permeable to K + and Cl ‐ but sparingly permeable to Na + . The absolute magnitude of the resting potential is similar to that calculated from the potassium concentrations if allowance is made for the contributions of chloride and other ions. Movements of K + and Cl ‐ as determined by radioactive tracers or by chemical methods agree with a quantitative formulation of this hypothesis. It is necessary to suppose that sodium is continuously pumped out of excitable cells by a process which depends on metabolism. Electrical activity is due to a large and specific increase in the permeability to sodium. The reversed potential difference across the active membrane arises from the concentration difference of sodium and varies with the external concentration of sodium in the same manner as the theoretical potential of a sodium electrode. In many cells, conduction of impulses is impossible if the external medium does not contain sodium or lithium ions. The rate of rise of the action potential varies with the concentration of sodium ions in the external medium. Sodium enters a nerve fibre when it is active. The quantity entering 1 cm. 2 of membrane during one impulse is of the order of 3 μμmol. Entry of sodium is approximately balanced by the leakage of a corresponding quantity of potassium. It is suggested that sodium enters the nerve fibre during the rising phase of the action potential and that potassium leaves during the falling phase. The permeability changes during the action potential probably consist of a rapid but transient increase in the permeability to sodium and a delayed increase in the permeability to potassium. It is suggested that both permeability changes vary with membrane potential in a graded but reversible manner. This hypothesis is applied to the phenomena of subthreshold activity, accomodation and oscillatory behaviour. In vertebrate myelinated fibres there is much evidence to show that conduction is saltatory; this suggests that sodium entry is confined to the nodes of Ranvier, and that the internodes are depolarized by local circuit action. Provided that nerves are not stimulated at a high rate, recovery heat production is sufficient to account for the metabolic extrusion of sodium after activity.