Differential modulation of Ca2+-activated K+ channels in ovine pituitary gonadotrophs by GnRH, Ca2+ and cyclic AMP

Patch-clamp techniques were employed to examine the effects of cAMP in relation to gonadotrophin-releasing hormone (GnRH) action on Ca2+-activated K+ channels in pituitary gonadotrophs derived from ovine pars tuberalis. GnRH applied extracellularly increased channel openings in cell-attached patches similar to calcium ionophore (A23187), while raising intracellular cAMP concentration with dibutyryl cAMP or forskolin decreased the number of functional channels (Nf) and the open state probability (Po). Both cAMP and the catalytic subunit of cAMP-dependent protein kinase produced similar results when applied to the cytoplasmic membrane face of inside-out patches, and the effect of cAMP was abolished by the protein kinase inhibitor. Our results suggest that decreased permeability through these channels modulated by cAMP through a phosphorylation-dependent route can modulate luteinizing hormone release.