Gambierol is a marine polycyclic ether toxin produced by the marine dinoflagellate Gambierdiscus toxicus. The present study examined the influence of gambierol on intact cerebrocortical neurons. Gambierol produced both a concentration-dependent augmentation of spontaneous Ca2+ oscillations and an inhibition of Kv channel function with similar potencies. Additionally, an array of selective Kv channel inhibitors mimicked gambierol in augmenting spontaneous Ca2+ oscillations in cerebrocortical neurons. These data are consistent with a gambierol blockade of Kv channels underlying the observed increase in spontaneous Ca2+ oscillation frequency. Furthermore, these results showed that gambierol produced a concentration-dependent stimulation of neurite outgrowth that was mimicked by 4-aminopyridine, a universal potassium channel inhibitor. Considered together, these data demonstrate that gambierol alters both Ca2+ signaling and neurite outgrowth in cerebrocortical neurons as a consequence of blockade of Kv channels.
See article at J Pharmacol Exp Ther 2014, 350:615–623.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics