Vinpocetine-induced stimulation of calcium-activated potassium currents in rat pituitary GH3 cells

Sheng Nan Wu, Hui Fang Li, Hung Ting Chiang

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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 μM) reversibly increased the amplitude of Ca2+-activated K+ current (IK(Ca)) with an EC50 value of 4 μM. When the recording pipettes were filled with 10 mM EGTA, vinpocetine also stimulated IK(Ca). In the cell-attached configuration, application of vinpocetine to the bath increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels. In excised membrane patches, application of vinpocetine (10 μM) to the bath did not change the single-channel conductance of BKCa channels; however, it did increase channel activity. In the inside-out configuration, neither 8-bromo cyclic GMP nor YC-1 applied intracellularly affected BKCa channel activity. The vinpocetine-induced change in the kinetic behavior of BKCa channels was due to an increase in mean open time and a decrease in mean closed time. Vinpocetine (10 μM) caused a leftward shift in the midpoint for the voltage-dependent opening. Under the current-clamp mode, vinpocetine (10 μM) decreased the firing rate of spontaneous action potentials induced by thyrotropin-releasing hormone (10 μM) in GH3 cells. In pheochromocytoma PC12 cells, vinpocetine (10 μM) applied intracellularly also enhanced the activity of BKCa channels without altering single-channel conductance. Thus, the present study suggests that vinpocetine-mediated stimulation of IK(Ca) may result from the direct activation of BKCa channels and indirectly from elevated cytosolic Ca2+.

Original languageEnglish
Pages (from-to)877-892
Number of pages16
JournalBiochemical Pharmacology
Volume61
Issue number7
DOIs
Publication statusPublished - 2001 Apr 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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