Vinpocetine-induced stimulation of calcium-activated potassium currents in rat pituitary GH3 cells.
The effects of vinpocetine, an inhibitor of cyclic GMP phosphodiesterase, on ionic currents were examined in rat pituitary GH3 lactotrophs with the aid of the patch-clamp technique. In GH3 cells bathed in normal Tyrode's solution, vinpocetine (10 microM) reversibly increased the amplitude of Ca2+-activated K+ current (I(K)Ca) with an EC50 value of 4 microM. When the recording pipettes were filled with 10 mM EGTA, vinpocetine also stimulated I(K)Ca. In the cell-attached configuration, application of vinpocetine to the bath increased the activity of large-conductance Ca2+-activated K+ (BK(Ca)) channels. In excised membrane patches, application of vinpocetine (10 microM) to the bath did not change the single-channel conductance of BK(Ca) channels; however, it did increase channel activity. In the inside-out configuration, neither 8-bromo cyclic GMP nor YC-1 applied intracellularly affected BK(Ca) channel 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 microM) caused a leftward shift in the midpoint for the voltage-dependent opening. Under the current-clamp mode, vinpocetine (10 microM) decreased the firing rate of spontaneous action potentials induced by thyrotropin-releasing hormone (10 microM) in GH3 cells. In pheochromocytoma PC12 cells, vinpocetine (10 microM) applied intracellularly also enhanced the activity of BK(Ca) 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 BK(Ca) channels and indirectly from elevated cytosolic Ca2+.
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, 813, Kaohsiung City, Taiwan. snwu@isca.vghks.gov.tw
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D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004347:Drug Interactions; D004594:Electrophysiology; D020536:Enzyme Activators / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007700:Kinetics; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D014407:Tumor Cells, Cultured; D014748:Vinca Alkaloids / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020536:Enzyme Activators; D007191:Indazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D014748:Vinca Alkaloids; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; C016276:8-bromocyclic GMP; C013983:vinpocetine; D006152:Cyclic GMP