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

**Evelyne Benoit 1,2, Sébastien Schlumberger 2, Jordi Molgó 1,2,\*, Makoto Sasaki 3, Haruhiko Fuwa <sup>4</sup> and Roland Bournaud 2,\***


**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<sup>+</sup> current and slowed the kinetics of K+ current activation. The use of selective channel blockers disclosed that gambierol did not affect calciumactivated K<sup>+</sup> (KCa) and ATP-sensitive K<sup>+</sup> (KATP) channels. The gambierol concentration necessary to inhibit 50% of the K<sup>+</sup> 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:** fetal adrenomedullary chromaffin cell; gambierol; potassium currents; calcium-activated K+ channels; ATP-sensitive K+ channels; catecholamine release

**Key Contribution:** The study enhances the knowledge we have on the several types of K<sup>+</sup> channels contributing to the total outward current of rat fetal (F19–F20) chromaffin cells lacking splanchnic innervation, and shows that gambierol, a dinoflagellate polyether toxin, affects only a K+ current fraction, distinct to the KCa and KATP currents, and has no action on Ca2+-dependent catecholamine secretion. The results further highlight the key modulatory role played by KCa currents in the control of exocytosis at this fetal stage.
