Software-based correction of single compartment series resistance errors

Abstract

Resistance across a patch pipette following seal formation and attainment of the whole cell recording configuration can introduce considerable and sometimes non-intuitive errors into voltage clamp recordings. These errors can be corrected actively on most commercially available amplifiers, although decisions during the experiment often must be made concerning the degree of correction to be employed, and the decision is essentially irreversible once the data is recorded. Amplifier-based corrections assume a single compartment, and thus any degree of compensation could be applied after data collection with a delay of only a single digitization interval. This report describes computer algorithms that correct capacitative filtering that results from pipette series resistance as well as the voltage error for current responses with either linear or non linear current–voltage curves. The algorithms are designed to operate on data that are recorded at a single holding potential rather than in response to voltage steps. The simplest algorithm for correction of responses with linear IV consists of about a dozen lines of C code and can easily be incorporated into data analysis programs, spreadsheets, and mathematical analysis packages. Code, sample programs, and spreadsheets that implement these algorithms are available from ftp.pharm.emory.edu.