Title

Quinine Decreases Hepatocyte Transmembrane Potential and Inhibits Amino Acid Transport

Document Type

Article

Publication Date

1-1-1988

Description

Effects of L-alanine, 2-(methylamino)isobutyric acid (MeAIB), and quinine on mouse hepatocyte transmembrane potential (V(m)) 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 V(m) 6 ± 0.4 mV from control V(m) (-37 ± 0.2 mV). With L-alanine still present, V(m) repolarized and stabilized at V(m) of -2 ± 0.5 mV greater than control V(m). Quinine (1 mM) decreased V(m) reversibly by 7 ± 0.9 mV. Depolarization was 11 ± 1.5 mV when L-alanine and quinine were added together, but now V(m) 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 V(max) 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 K(m) 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 μl/mg protein. Thus quinine may inhibit Na+-amino acid cotransport by blocking conductive K+ channels, thereby decreasing V(m) and the transmembrane electrochemical Na+ gradient, and it may deplete the intracellular amino acid pool by disrupting hepatocyte volume regulation.

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