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 (Ip) measurements. First, the steady-state characteristics of activation (x infinity) and inactivation (z infinity) must be estimated, and it is shown that Ip 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 << 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 (g) values, and a tau x/tau z ratio that relates x infinity and z infinity to the Ip data. When additional information is available, such as the time of occurrence of Ip or an estimate of tau z from the late portion of the ionic current response, one can narrow down the value of g 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.