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  2. Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells

Gambierol Blocks a K+ Current Fraction without Affecting Catecholamine Release in Rat Fetal Adrenomedullary Cultured Chromaffin Cells

  • Toxins (Basel). 2022 Apr 2;14(4):254. doi: 10.3390/toxins14040254.
Evelyne Benoit 1 2 Sébastien Schlumberger 2 Jordi Molgó 1 2 Makoto Sasaki 3 Haruhiko Fuwa 4 Roland Bournaud 2
Affiliations

Affiliations

  • 1 Service d'Ingénierie Moléculaire pour la Santé (SIMoS), Département Médicaments et Technologies pour la Santé (DMTS), Institut des Sciences du Vivant Frédéric Joliot, Université Paris-Saclay, CEA, INRAE, ERL CNRS 9004, F-91191 Gif-sur-Yvette, France.
  • 2 CNRS, Laboratoire de Neurobiologie Cellulaire et Moléculaire-UPR 9040, F-91198 Gif-sur-Yvette, France.
  • 3 Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan.
  • 4 Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo 112-8551, Japan.
Abstract

Gambierol inhibits voltage-gated K+ (KV) channels in various excitable and non-excitable cells. The purpose of this work was to study the effects of gambierol on single rat fetal (F19-F20) adrenomedullary cultured chromaffin cells. These excitable cells have different types of KV channels and release catecholamines. Perforated whole-cell voltage-clamp recordings revealed that gambierol (100 nM) blocked only a fraction of the total outward K+ current and slowed the kinetics of K+ current activation. The use of selective channel blockers disclosed that gambierol did not affect calcium-activated K+ (KCA) and ATP-sensitive K+ (KATP) channels. The gambierol concentration necessary to inhibit 50% of the K+ current-component sensitive to the polyether (IC50) was 5.8 nM. Simultaneous whole-cell current-clamp and single-cell amperometry recordings revealed that gambierol did not modify the membrane potential following 11s depolarizing current-steps, in both quiescent and active cells displaying repetitive firing of action potentials, and it did not increase the number of exocytotic Catecholamine release events, with respect to controls. The subsequent addition of apamin and iberiotoxin, which selectively block the KCA channels, both depolarized the membrane and enhanced by 2.7 and 3.5-fold the exocytotic event frequency in quiescent and active cells, respectively. These results highlight the important modulatory role played by KCA channels in the control of exocytosis from fetal (F19-F20) adrenomedullary chromaffin cells.

Keywords

ATP-sensitive K+ channels; calcium-activated K+ channels; catecholamine release; fetal adrenomedullary chromaffin cell; gambierol; potassium currents.

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