Hydrogen sulfide induces hyperpolarization and decreases the exocytosis of secretory granules of rat GH3 pituitary tumor cells

Abstract

© 2015 Elsevier Inc. All rights reserved. The aim of the present study was to evaluate the effects of hydrogen sulfide (H<inf>2</inf>S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H<inf>2</inf>S donor - sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC<inf>50</inf> of 152 μM (equals effective H<inf>2</inf>S of 16-19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (K<inf>ATP</inf>) by glibenclamide or by diazoxide, respectively. In whole-cell recordings NaHS increased the amplitude of K<inf>ATP</inf> currents, induced by hyperpolarizing pulses and subsequent application of glibenclamide decreased currents to control levels. Using the fluorescent dye FM 1-43 exocytosis of secretory granules was analyzed in basal and stimulated conditions (high K⁺ external solution). Prior application of NaHS decreased the fluorescence of the cell membrane in both conditions which links with activation of K<inf>ATP</inf> currents (basal secretion) and activation of K<inf>ATP</inf> currents and BK-currents (stimulated exocytosis). We suggest that H<inf>2</inf>S induces hyperpolarization of GH3 cells by activation of K<inf>ATP</inf> channels which results in a truncation of spontaneous action potentials and a decrease of hormone release.