T H E Control of Membrane Ionic Currents by T H E Membrane Potential of Muscle*

Comparisons between electrotronic potentials and certain predicted curves allow the identification of the membrane potential at which the sodium and potassium currents are switched on in frog sartorins. The activation potentials (the membrane potentials at which the ionic currents are great enough to be resolved by the method) are functions of the resting potential and time but not of ionic concentration. In the normal fiber, the activation potential for sodium lies nearer the resting potential and depolarizations set off sodium currents and action potentials. Below a resting potential of 55 to 60 my. sodium activation is lost and conduction is impossible. A tenfold increase of calcium concentration lowers (moves further from the resting potential) the sodium activation potential by 20 to 25 Inv. whereas the potassium activation potential is lowered by only 15 inv. Certain consequences of this are seen in the behavior of the muscle cell when it is stimulated with long duration shock. The action potential appears to be generated by various voltageand timedependent changes of membrane conductance. The initiating step, sodium activation (an increase of the membrane's sodium conductance), begins when the membrane potential is reduced by electrical shock or advancing action potential to some characteristic value below the resting level, As the stimulus further depolarizes, activation increases until the restoring forces are overcome and the potential is driven toward the peak of the spike by the large, initial sodium current. There is, until this point is reached, a range of potential in which activation is present but not great enough to be regenerative. In this region are found local responses; these are the subject of this investigation. The striated muscle fiber has not yet yielded to voltage clamp techniques. Certain other procedures can be employed which allow the identification of sodium and potassium activation. Indications of the rates and magnitudes of * This work was made possible by a research grant (B-861) from the National Institute of Neurological Diseases and Blindness. Present address: Division of General Medical Sciences, National Institutes of Health, Bethesda.