RT Journal Article SR Electronic T1 Cav1.3 Is Preferentially Coupled to Glucose-Stimulated Insulin Secretion in the Pancreatic β-Cell Line INS-1 JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 271 OP 278 DO 10.1124/jpet.102.046334 VO 305 IS 1 A1 Guohong Liu A1 Nejmi Dilmac A1 Nathan Hilliard A1 Gregory H. Hockerman YR 2003 UL http://jpet.aspetjournals.org/content/305/1/271.abstract AB L-Type Ca2+ channel blockers inhibit glucose and KCl-stimulated insulin secretion by pancreatic β cells. However, the role of the two distinct L-type channels expressed by β cells, Cav1.2 and Cav1.3, in this process is not clear. Therefore, we stably transfected INS-1 cells with two mutant channel constructs, Cav1.2DHPi or Cav1.3 DHPi. Whole-cell patch-clamp recordings demonstrated that both mutant channels are insensitive to dihydropyridines (DHPs), but are blocked by diltiazem. INS-1 cells expressing Cav1.3/DHPi maintained glucose- and KCl-stimulated insulin secretion in the presence of DHPs, whereas cells expressing Cav1.2/DHPi demonstrated DHP resistance to only KCl-induced secretion. INS-1 cells were also stably transfected with cDNAs encoding the intracellular loop between domains II and III of either Cav1.2 or Cav1.3 (Cav1.2/II-III or Cav1.3/II-III). Glucose- and KCl-stimulated insulin secretion in Cav1.2/II-III cells were not different from untransfected INS-1 cells. However, glucose-stimulated insulin secretion was completely inhibited and KCl-stimulated secretion was substantially resistant to inhibition by DHPs, but sensitive to ω-agatoxin IVA in Cav1.3/II-III cells. Moreover, the L-type channel agonist FPL 64176 markedly enhanced KCl-stimulated secretion by Cav1.3/II-III cells. Together, our results suggest that Ca2+ influx via Cav1.3 is preferentially coupled to glucose-stimulated insulin secretion in INS-1 cells. The American Society for Pharmacology and Experimental Therapeutics