ON THE INTERPRETATION OF VOLTAGE-CLAMP DATA USING THE HODGKIN-HUXLEY MODEL

This paper describes a method to extract membrane model parameters from experimental voltage-clamp records. The underlying theory is based on two premises: (1) the membrane dynamics can be described by a Hodgkin-Huxley (HH) model, and (2) the most reliable data provided by voltage clamp experiments are peak current (I(p)) measurements. First, the steady-state characteristics of activation (x(infinity)) and inactivation (z(infinity)) must be estimated, and it is shown that I(p) data provided by standard voltage-clamp stimulation protocols are sufficient for this purpose for the case of well-separated activation (tau(x)) and inactivation (tau(z)) time constants, tau(x) much less than tau(z). Next, we propose a test (R test) to establish the suitability of the HH model to represent the data. When the HH model is applicable (successful R test), the procedure yields the degree of the gating variables, a range of maximum membrane conductance (gBAR) values, and a tau(x)/tau(z) ratio that relates x(infinity) and z(infinity) to the I(p) data. When additional information is available, such as the time of occurrence of I(p) or an estimate of tau(z) from the late portion of the ionic current response, one can narrow down the value of gBAR and estimate all the HH parameters and functions. Otherwise, when the R test is not successful, one can conclude that x(infinity) and z(infinity) have been incorrectly estimated because tau(x) and tau(z) are not sufficiently separated or that the HH model is not applicable to the data.