Quinine decreases hepatocyte transmembrane potential and inhibits amino acid transport

Abstract

Effects of L-alanine, 2-(methylamino)isobutyric acid (MeAIB), and quinine on mouse hepatocyte transmembrane potential (Vm) are compared with effects of quinine on MeAIB transport into isolated mouse hepatocytes in primary monolayer culture. In liver slices, L-alanine (10 mM) decreased Vm 6 +/- 0.4 mV from control Vm (-37 +/- 0.2 mV). With L-alanine still present, Vm repolarized and stabilized at Vm of -2 +/- 0.5 mV greater than control Vm. Quinine (1 mM) decreased Vm reversibly by 7 +/- 0.9 mV. Depolarization was 11 +/- 1.5 mV when L-alanine and quinine were added together, but now Vm did not repolarize. Transient depolarization also resulted from addition of either L-alanine or MeAIB to isolated hepatocytes in primary culture. Moreover, quinine (1 mM) inhibited steady-state MeAIB uptake by 91%. Quinine decreased Vmax for MeAIB transport from 9.0 +/- 1.0 to 4.8 +/- 1.9 nmol MeAIB.mg protein-1.4 min-1, but it did not change Km of 0.60 mM. Quinine inhibition of MeAIB transport was reversible. Quinine also increased hepatocyte steady-state volume from 3.2 +/- 0.8 to 4.9 +/- 1.2 microliter/mg protein. Thus quinine may inhibit Na+-amino acid cotransport by blocking conductive K+ channels, thereby decreasing Vm and the transmembrane electrochemical Na+ gradient, and it may deplete the intracellular amino acid pool by disrupting hepatocyte volume regulation.