Modulation of gonadotropin II release by K+ channel blockers in goldfish gonadotropes: a novel stimulatory action of 4-aminopyridine.
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.
Wong
C J
CJ
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Kwong
P
P
Johnson
J D
JD
Yunker
W K
WK
Chang
J P
JP
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D016257:Fura-2; D006054:Goldfish; D006065:Gonadotropins, Pituitary / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005456:Fluorescent Dyes; D006065:Gonadotropins, Pituitary; D010726:Phosphodiesterase Inhibitors; D026902:Potassium Channel Blockers; D002110:Caffeine; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D014700:Verapamil; D002118:Calcium; D016257:Fura-2