Referenced in: none

Automatically associated channels: Cav1.3 , Slo1

Title: Cav1.3 is preferentially coupled to glucose-induced [Ca2+]i oscillations in the pancreatic beta cell line INS-1.

Authors: Guohong Liu, Nathan Hilliard, Gregory H Hockerman

Journal, date & volume: Mol. Pharmacol., 2004 May , 65, 1269-77

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15102955

Abstract
The link between Ca(2+) influx through the L-type calcium channels Ca(v)1.2 or Ca(v)1.3 and glucose- or KCl-induced [Ca(2+)](i) mobilization in INS-1 cells was assessed using the calcium indicator indo-1. Cells responded to 18 mM glucose or 50 mM KCl stimulation with different patterns in [Ca(2+)](i) increases, although both were inhibited by 10 microM nifedipine. Although KCl elicited a prolonged elevation in [Ca(2+)](i), glucose triggered oscillations in [Ca(2+)](i.) Ca(v)1.2/dihydropyridine-insensitive (DHPi) cells and Ca(v)1.3/DHPi cells, and stable INS-1 cell lines expressing either DHP-insensitive Ca(v)1.2 or Ca(v)1.3 channels showed normal responses to glucose. However, in 10 microM nifedipine, only Ca(v)1.3/DHPi cells maintained glucose-induced [Ca(2+)](i) oscillation. In contrast, both cell lines exhibited DHP-resistant [Ca(2+)](i) increases in response to KCl. The percentage of cells responding to glucose was not significantly decreased by nifedipine in Ca(v)1.3/DHPi cells but was greatly reduced in Ca(v)1.2/DHPi cells. In 10 microM nifedipine, KCl-elicited [Ca(2+)](i) elevation was retained in both Ca(v)1.2/DHPi and Ca(v)1.3/DHPi cells. In INS-1 cells expressing the intracellular II-III loop of Ca(v)1.3, glucose failed to elicit [Ca(2+)](i) changes, whereas INS-1 cells expressing the Ca(v)1.2 II-III loop responded to glucose with normal [Ca(2+)](i) oscillation. INS-1 cells expressing Ca(v)1.2/DHPi containing the II-III loop of Ca(v)1.3 demonstrated a nifedipine-resistant slow increase in [Ca(2+)](i) and nifedipine-resistant insulin secretion in response to glucose that was partially inhibited by diltiazem. Thus, whereas the II-III loop of Ca(v)1.3 may be involved in coupling Ca(2+) influx to insulin secretion, distinct structural domains are required to mediate the preferential coupling of Ca(v)1.3 to glucose-induced [Ca(2+)](i) oscillation.