Letter to the editor: Accurate cell capacitance determination from a single voltage step: a reminder to avoid unnecessary pitfalls.

TO THE EDITOR: Cell membrane capacitance Cm is a fundamental property of excitable cells. It scales with the cell surface area and is therefore used for cell size estimation and most important for normalizing currents and conductances. Consequently, proper knowledge of Cm is also crucial for accurate cell modeling (7). Whole cell patch-clamp technique has led to the development of elaborate methods for Cm estimation (3). Among the voltage clamp-based approaches, step response analysis is often the method of choice (Fig. 1, A and B). A mandatory requirement for accurate Cm determination during voltage-clamp steps is that changes in membrane resistance Rm are negligible (8). Accuracy also depends on the choice of the analysis method of the current transient. Considering Grubb et al. (4) and Vaidyanathan et al. (6), published in two previous issues of the American Journal of Physiology-Heart and Circulatory Physiology, and from other publications (2, 9), we want to point out that straightforward integration of the current transient and subsequent division by the commanded voltage step E, as frequently used, is prone to give incorrect Cm estimates and how this can be avoided by proper approximating charge Q and membrane voltage Vm at the cell membrane. Obviously, it is still common practice to determine Cm by application of a small voltage-clamp step E (Fig. 1B) and to numerically integrate the current response to the new steady state to get the charge Q under the current transient by