Vinpocetine-induced stimulation of calcium-activated potassium currents inrat pituitary GH(3) cells

The effects of vinpocetine, an inhibitor of cyclic GMP phosphodiesterase, o n ionic currents were examined in rat pituitary GH(3) lactotrophs with the aid of the patch-clamp technique. In GH(3) cells bathed in normal Tyrode's solution, vinpocetine (10 muM) reversibly increased the amplitude of Ca2+-a ctivated K+ current (I-K(Ca))with an EC50 value of 4 muM. When the recordin g pipettes were filled with 10 mM EGTA, vinpocetine also stimulated I-K(Ca) . In the cell-attached configuration, application of vinpocetine to the bat h increased the activity of large-conductance Ca2+-activated K+ (BKCa) chan nels. In excised membrane patches, application of vinpocetine (10 muM) to t he bath did not change the single-channel conductance of BKCa channels; how ever, it did increase channel activity. In the inside-out configuration, ne ither 8-bromo cyclic GMP nor YC-1 applied intracellularly affected BKCa cha nnel activity. The vinpocetine-induced change in the kinetic behavior of BK Ca channels was due to an increase in mean open time and a decrease in mean closed time. Vinpocetine (10 muM) caused a leftward shift in the midpoint for the voltage-dependent opening. Under the current-clamp mode, vinpocetin e (10 muM) decreased the firing rate of spontaneous action potentials induc ed by thyrotropin-releasing hormone (10 muM) in GH(3) cells. In pheochromoc ytoma PC12 cells, vinpocetine (10 muM) applied intracellularly also enhance d the activity of BKCa channels without altering single-channel conductance . Thus, the present study suggests that vinpocetine-mediated stimulation of I-K(Ca) may result from the direct activation of BKCa channels and indirec tly from elevated cytosolic Ca2+. (C) 2001 Elsevier Science Inc. All rights reserved.