Transmembrane potentials in guinea-pig hepatocytes

1. In pieces of guinea-pig liver with an intact capsule, the mean resting potential (E) is -49.8 mV, close to the value for in vivo hepatocytes and significantly higher than a similar preparation of rat liver. E is considerably less than the calculated K equilibrium potential of about -90 mV.2. Changes in [K(+)](o) in the range of 0-10 mM produce almost no change in E. At [K(+)](o) above 20 mM, a tenfold increase produces only a 33 mV depolarization. The results with changing [K(+)](o) are the same in Cl(-) free solutions (isethionate substitution) or when the [K(+)](o)[Cl(-)](o) product is kept constant. E rapidly returned to normal in liver pieces returned to Ringer after prolonged soaking in high K(+) solution.3. Changes in [Na(+)](o), [Cl(-)](o), [H(+)](o), [Ca(2+)](o) or [Mg(2+)](o) have little effect on E. Simultaneous variation of [Na(+)](o) and [Cl(-)](o) in opposite directions to maximize predicted changes in E also has only a minimal effect on E.4. Cyanide (5 mM) or ouabain (10(-4)M) cause depolarization, so there is no reason to believe that pumps sensitive to these poisons are normally lowering resting potential. Part of the normal E may be produced by an electrogenic ouabain-sensitive ion pump.5. The data is interpreted by using a form of the constant field equation developed by Brading & Caldwell (1971). Application of this method yields P(Na)/P(K) less than 0.04, P(Cl)/P(K) approximately 0.3. Additional terms, x and y, are required to account for the behaviour of E. Their physical basis remains undetermined.6. Suggestions are presented for further study and for the application of the method of Brading & Caldwell to other non-excitable cells and to excitable cells in low [K(+)](o), in which E is poorly understood.