Potassium current suppression by quinidine reveals additional calcium currents in neuroblastoma cells.

Abstract

Quinine and quinidine were evaluated with regard to their effects on the electrical activity of neuroblastoma cells [mouse neuroblastoma NIE-115 cells and mouse neuroblastoma-rat glioma hybrid NG108-15 cells]. Under voltage-clamp conditions, quinine and quinidine block both the voltage-dependent and Ca2+-dependent K+ conductances. Blockage of the voltage-dependent K+ channel is manifest as an increase in the amplitude and in the duration of the action potential. Blockage of the Ca2+-dependent K+ channel in Na+-free (replaced by Tris) solutions containing 6.8 mM Ca2+ and tetraethylammonium ion, or 4-aminopyridine (to block the voltage-dependent K+ current), is a further prolongation of the Ca2+ action potential and diminution of the afterhyperpolarization. A critical role of the Ca2+ dependent K+ conductance in modulation of the rate and duration of trains of Ca2+ action potentials is shown by the use of low concentrations (5-40 .mu.M) of quinine or quinidine, which diminish the Ca2+-dependent K+ conductance in a graded manner. After complete blockade of K+ currents, the peak Ca2+ currents are enhanced at all voltages, especially at values more positive than -30 mV, where a steady-state inward current appears. In this same voltage range, the decay of the Ca2+ currents exhibits 2 time constants.sbd.that of the transient inward current, which is .apprx. 20 ms, and a much slower (.apprxeq. 2000 ms) component. Neuroblastoma cells may have 2 types of Ca channels: one generates the Ca2+ action potential and a 2nd, distinguished by activation at more depolarized levels and by a slow rate of inactivation, underlies the Ca entry necessary to activate the Ca2+-dependent K+ conductance.