Supercharging: a method for improving patch-clamp performance

Abstract

Patch-clamp performance can be improved without altering the normal headstage configuration described by (Hamill, O. P., A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth, 1981, Pfluegers Arch. Eur. J. Physiol., 391:85-100). The "supercharging" method permits resolution of such fast events as calcium and sodium tail currents. Digital computer modeling and analog electronic simulation were used to identify appropriate shapes for the command voltage and the voltage applied to a capacitor tied to the input of the headstage. The voltage command pulse consists of a step with a brief (5-15 microseconds) rectangular spike on its leading edge. Spike amplitude is a function of the membrane capacitance and the access resistance. The spike drives current through the access resistance and speeds charging of the membrane capacitance, making it possible to complete a voltage step within 5-15 microseconds. Clamping speed is independent of the electrode and feedback resistance over a wide range. The second function of the patch clamp amplifier is current measurement, and good time resolution requires suppression of the capacity transient. This can be accomplished by applying an appropriately shaped voltage to the small capacitor tied to the input of the headstage. Series resistance compensation for ionic current transients does not interfere with supercharging. Although the focus of this paper is on whole cell recording, the supercharging concept may prove useful for single channel and bilayer recording techniques.