Switched single-electrode voltage-clamp amplifiers allow precise measurement of gap junction conductance

Measurement of gap junction conductance (g(j)) with patch-clamp amplifiers can, due to series resistance problems, be subject to considerable errors when large currents are measured. Formulas developed to correct for these errors unfortunately depend on exact estimates of series resistance, which are not always easy to obtain. Discontinuous single-electrode voltage-clamp amplifiers (DSEVCs) were shown to overcome series resistance problems in single whole cell recording. With the use of two synchronized DSEVCs, the simulated g(j) in a model circuit can be measured with a maximum error of <5% in all recording situations investigated (series resistance, 5-47 M Omega; membrane resistance, 20-1,000 M Omega; g(j), 1-100 nS). At a very low g(j) of 100 pS, the error sometimes exceeded 5% (maximum of 15%), but the error was always <5% when membrane resistance was >100 M Omega. The precision of the measurements is independent of series resistance, membrane resistance, and g(j). Consequently, it is possible to calculate g(j) directly from Ohm's law, i.e., without using correction formulas. Our results suggest that DSEVCs should be used to measure g(j) if large currents must be recorded, i.e., if cells are well coupled or if membrane resistance is low.