A Novel Method to Quantify Contribution of Channels and Transporters to Membrane Potential Dynamics

The action potential, once triggered in ventricular or atrial myocytes, automatically proceeds on its time course or is generated spontaneously in sinoatrial node pacemaker cells. It is induced by complex interactions among such cellular components as ion channels, transporters, intracellular ion concentrations, and signaling molecules. We have developed what is, to our knowledge, a new method using a mathematical model to quantify the contribution of each cellular component to the automatic time courses of the action potential. In this method, an equilibrium value, which the membrane potential is approaching at a given moment, is calculated along the time course of the membrane potential. The calculation itself is based on the time-varying conductance and the reversal potentials of individual ion channels and electrogenic ion transporters. Since the equilibrium potential moves in advance of the membrane potential change, we refer to it as the lead potential, V_L. The contribution of an individual current was successfully quantified by comparing dV_L/dt before and after fixing the time-dependent change of a component of interest, such as the variations in the open probability of a channel or the turnover rate of an ion transporter. In addition to the action potential, the lead-potential analysis should also be applicable in all types of membrane excitation in many different kinds of cells.