Characterization of the effects of a new Ca2+ channel activator, FPL 64176, in GH3 cells
Kunze, D.L.; Rampe, D.
Molecular Pharmacology 42(4): 666-670
1992
ISSN/ISBN: 0026-895X PMID: 1279375 Document Number: 394614
We examined the effects of the benzoylpyrrole-type Ca-2+ channel activator FPL 64176 on voltage-dependent L-type Ca-2+ channels in rat anterior pituitary (GH-3) cells. FPL 64176 increased K+dependent Ca-2+ influx into GH-3 cells with an EC-50 value of 1.2 times 10-7 M but had no effect on the binding of (3H)PN200-110 to GH-3 cell membranes at concentrations up to 10-6 M. Whole-cell patch-clamp electrophysiology revealed that FPL 64176 (1 mu-M) increased L-type Ca-2+ channel current amplitude and shifted the current-voltage relationship in the hyperpolarizing direction. Furthermore, Ca-2+ channel current activation and deactivation were prolonged. Single-channel analysis showed that FPL 64176 increased both the probability of channel opening and the mean channel open time. Interestingly, the effect of FPL 64176 on channel open time was highly voltage dependent, with much longer openings being observed at more hyperpolarized potentials. We conclude that FPL 64176 represents a new class of L-type Ca-2+ channel activator with a novel site and mechanism of action.