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

This paper describes a method to extract membrane model parameters fro m experimental voltage-clamp records. The underlying theory is based o n two premises: (1) the membrane dynamics can be described by a Hodgki n-Huxley (HH) model, and (2) the most reliable data provided by voltag e clamp experiments are peak current (I(p)) measurements. First, the s teady-state characteristics of activation (x(infinity)) and inactivati on (z(infinity)) must be estimated, and it is shown that I(p) data pro vided by standard voltage-clamp stimulation protocols are sufficient f or this purpose for the case of well-separated activation (tau(x)) and inactivation (tau(z)) time constants, tau(x) much less than tau(z). N ext, we propose a test (R test) to establish the suitability of the HH model to represent the data. When the HH model is applicable (success ful R test), the procedure yields the degree of the gating variables, a range of maximum membrane conductance (gBAR) values, and a tau(x)/ta u(z) ratio that relates x(infinity) and z(infinity) to the I(p) data. When additional information is available, such as the time of occurren ce 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 be en incorrectly estimated because tau(x) and tau(z) are not sufficientl y separated or that the HH model is not applicable to the data.