Two stable levels of diastolic potential at physiological K+ concentrations in human ventricular myocardial cells.

Abstract

Cells in many specimens of human ventricle can exhibit either of two stable levels of diastolic potential (DP) when exposed to 4 mM K+ in vitro (i.e., -78 +/- 4 mV or -45 +/- 5 mV, mean +/- SEM). In this report we show that the DP of some partially depolarized human ventricular cells developed a sustained 25-35 mV hyperpolarization (n = 28) when bath K+ concentration (K+b) was raised from 4 to 7 mM. On return of K+b to 4 mM, the DP of most, but not all, of these cells returned to the original depolarized levels. In other cells, the transition between the two levels of DP occurred at variable K+b ranging from 1 to 20 mM. We investigated the ionic mechanism(s) underlying the shifts between the two levels of potential by studying the K+ dependence of the DP in partially depolarized cells in 22 specimens of human ventricle. DP hyperpolarized an average of 25.6 mV (from -44.4 +/- 1.3 to -70.0 +/- 1.3 mV; n = 25) when K+b was increased from 4 to 7 mM. Intracellular K+ activity, determined by K+-selective microelectrodes, was within the range of normal reported for other mammalian species (106.7 +/- 4.4 mM in 4 mM K+; n = 22) and was unaffected by increasing K+b to 7 mM (111.7 +/- 6.6 mM; n = 6). Ba2+ (0.05 mM), a blocker of the inward rectifying K+ current, reversibly prevented the hyperpolarization, whereas acetylstrophanthidin (9 microM) failed to inhibit it. These results suggest that the hyperpolarization was due to a K+-dependent increase in K+ permeability and that electrogenic sodium pumping did not contribute significantly to the process. The ionic basis of the depolarization from a hyperpolarized level of DP also was investigated. Decreasing bath Na+ concentration and exposure to 30 microM tetrodotoxin did not prevent the depolarization. However, the depolarization could be inhibited by 2 mM Mn2+. These findings suggest that the depolarization may have been due to a Mn2+-sensitive inward current.