Modulation of gonadotropin II release by K+ channel blockers in goldfish gonadotropes: a novel stimulatory action of 4-aminopyridine.

Abstract

The effects of K+ channel blockers on basal gonadotropin II (GTH-II) release were examined in cultured goldfish gonadotropes. Tetraethylammonium (TEA) inhibited basal GTH-II release, whereas 4-aminopyridine (4-AP) increased basal release, although both K+ channel blockers generated increases in [Ca2+]i. Other K+ channel blockers had no significant effect on GTH-II release. We examined whether Ca2+ entry that arises from blockade of K+ channels by 4-AP mediates the secretory response. Secretion evoked by 4-AP was slightly reduced by TEA but was unaffected by reducing Ca2+ entry using either an inhibitor of Ca2+ channels, verapamil, or nominally Ca2+-free medium. In contrast, the Ca2+ signal evoked by 4-AP was largely blocked by Ca2+-free medium, as predicted by its inhibitory action on K+ channels. Together, these data suggest that the hormone release response to 4-AP is independent of entry of extracellular Ca2+. Finally, the mechanism of hormone release evoked by 4-AP appeared to be independent of mechanism(s) evoked by caffeine since 4-AP did not affect caffeine-evoked release and caffeine did not affect 4-AP evoked release. That both 4-AP and TEA generated Ca2+ signals but affected hormone release in either an extracellular Ca2+ independent (4-AP) or inhibitory (TEA) manner suggests that Ca2+ entry is linked to GTH-II secretion in a highly nonlinear fashion.