This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre (Hodgkin, Huxley & Katz, 1952; Hodgkin & Huxley, 1952 a-c). Its general object is to discu the results of the preceding papers (Part I), to put them into mathematical form (Part II) and to show that they will account for conduction and excitation in quantitative terms (Part III).PART I. DISCUSSION OF EXPERIMENTAL RESULTS The results described in the preceding papers suggest that the electrical behaviour of the membrane may be represented by the network shown in Fig. 1. Current can be carried through the membrane either by charging the membrane capacity or by movement of ion-s through the resistances in parallel with the capacity. The ionic current is divided into components carried by sodium and potassium ions (INa and IK), and a small 'leakage current' (I,) made up by chloride and other ions. Each component of the ionic current is determined by a driving force which may conveniently be measured as an electrical potential difference and a permeability coefficient which has the dimensions of a conductance. Thus the sodium current (INa) is equal to the sodium conductance (9Na) multiplied by the difference between the membrane potential (E) and the equilibrium potential for the sodium ion (ENa). Similar equations apply to 'K and I, and are collected on p. 505.Our experiments suggest that gNa and 9E are functions of time and membrane potential, but that ENa, EK, El, CM and g, may be taken as constant. The influence of membrane potential on permeability can be summarized by stating: first, that depolarization causes a transient increase in sodium conductance and a slower but maintained increase in potassium conductance; secondly, that these changes are graded and that they can be reversed by repolarizing the membrane. In order to decide whether these effects are sufficient to account for complicated phenomena such as the action potential and refractory period, it is necessary to obtain expressions relating

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The most widely accepted theory of the restirng potential of muscle is that the electrical potential difference between the inside and outside of a muscle fibre arises from the concentration gradients of the potassium and chloride ions. If we follow Boyle & Conway (1941), the membrane is assumed to be permeable to K and Cl but to be impermeable or sparingly permeable to other ions. Since K is more concentrated inside and Cl is more concentrated outside, the interior of the fibre should be electrically negative to the external solution. If K and Cl are distributed passively, the concentration ratios and the membrane potential under equilibrium conditions ought to conform to the relationwhere [ ]O and [ ]i indicate concentrations outside and inside the fibre, V is the internal potential, F is Faraday's constant, R is the gas constant and T is the absolute temperature. When the external potassium concentration is less than 10 mm agreement with equation (1) is not perfect, but at higher concentrations the relation seems to hold with considerable accuracy (Adrian, 1956;Conway, 1957). However, it is only possible to calculate the membrane potential by equation (1) when the concentrations of K and Cl inside the fibre have come into equilibrium with those in the external solution. In order to deal with other situations one must know the relative conductances or permeabilities of the two ions. Information on this point can be obtained by measuring the effect on membrane potential of sudden changes in the concentrations of K or Cl. Such experiments are difficult to interpret unless the effect of changing the external solution can be determined in a time which is so short that there is no alteration in the internal concentration of Cl or K. The present observations were carried out with single muscle fibres, with an

In the preceding paper (Hodgkin, Huxley & Katz, 1952) we gave a general description of the time course of the current which flows through the membrane of the squid giant axon when the potential difference across the membrane is suddenly changed from its resting value, and held at the new level by a feed-back circuit ('voltage clamp' procedure). This article is chiefly concerned with the identity of the ions which carry the various phases of the membrane current.One of the most striking features of the records of membrane current obtained under these conditions was that when the membrane potential was lowered from its resting value by an amount between about 10 and 100 mV. the initial current (after completion of the quick pulse through the membrane capacity) was in the inward direction, that is to say, the reverse of the direction of the current which the same voltage change would have caused to flow in an ohmic resistance. The inward current was of the right order of magnitude, and occurred over the right range of membrane potentials, to be the current responsible for charging the membrane capacity during the rising phase of an action potential. This suggested that the phase of inward current in the voltage clamp records might be carried by sodium ions, since there is much evidence (reviewed by Hodgkin, 1951) that the rising phase of the action potential is caused by the entry of these ions, moving under the influence of concentration and potential differences. To investigate this possibility, we carried out voltage clamp runs with the axon surrounded by solutions with reduced sodium concentration. Choline was used as an inert cation since replacement of sodium with this ion makes the squid axon completely inexcitable, but does not

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