Cjh. Wong et al., Modulation of gonadotropin II release by K+ channel blockers in goldfish gonadotropes: A novel stimulatory action of 4-aminopyridine, J NEUROENDO, 13(11), 2001, pp. 951-958
The effects of K+ channel blockers on basal gonadotropin II (GTH-II) releas
e were examined in cultured goldfish gonadotropes. Tetraethylammonium (TEA)
inhibited basal GTH-II release, whereas 4-aminopyridine (4-AP) increased b
asal release, although both K+ channel blockers generated increases in [Ca2
+](i). Other K+ channel blockers had no significant effect on GTH-II releas
e. 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 sligh
tly reduced by TEA but was unaffected by reducing Ca2+ entry using either a
n 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 m
edium, as predicted by its inhibitory action on K+ channels. Together, thes
e data suggest that the hormone release response to 4-AP is independent of
entry of extracellular Ca2+. Finally, the mechanism of hormone release evok
ed by 4-AP appeared to be independent of mechanism(s) evoked by caffeine si
nce 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 aff
ected hormone release in either an extracellular Ca2+ independent (4-AP) or
inhibitory (TEA) manner suggests that Ca2+ entry is linked to GTH-II secre
tion in a highly nonlinear fashion.