Determination of cell capacitance using the exact empirical solution of partial derivativeY/partial derivativeCm and its phase angle

Measures of membrane capacitance offer insight into a variety of cellular processes. Unfortunately, popular methodologies rely on model simplifications that sensitize them to interference from inevitable changes in resistive components of the traditional cell-clamp model. Here I report on a novel method to measure membrane capacitance that disposes of the usual simplifications and assumptions, yet is immune to such interference and works on the millisecond timescale. It is based on the exact empirical determination of the elusive partial derivative, partial derivativeY/partial derivativeC(m), which heretofore had been approximated. Furthermore, I illustrate how this method extends to the vesicle fusion problem by permitting the determination of partial derivativeY(v)/partial derivativeC(v), thereby providing estimates of fusion pore conductance and vesicle capacitance. Finally, I provide simulation examples and physiological examples of how the method can be used to study processes that are routinely interrogated by measures of membrane capacitance.