Measurement of epithelial electrical characteristics with an automatic voltage clamp device with compensation for solution resistance

A device is described which provides continuous measurement of transepithelial currents in isolated intestine or other tissues while clamping the transmural potential difference at zero or at a predetermined value. With tissues such as intestine, where the apparent tissue resistivity is of the same order as that of the bathing solution between the potential measuring electrodes and the tissue surface, compensation for the IR voltage drop in the solution is required. Using operational amplifiers and a special feedback circuit to drive a summing junction to virtual ground, the device enforces the equation ET??EIR??EVC=0 where ET is the measured transmural potetial difference between a pair of reversible electrodes and EIR is the potential drop in the solution due to the transmural currrent IT. The clamped voltage across the tissue Evc is thus equal to the true transmural potential difference. The circuit employed provides for readout of ET, EIR, Evc, and IT with uncertties emof 0.2 mV and 0.2 ??A and a 90 percent response time of 0.1 second. Because of its rapid automatic response, this devie is especially useful for accurately following transient changes in IT following temperature changes or the addition of transported solutes, metabolites, hormones, or drugs to the bathing medium.