TRPM4 impacts on Ca2+ signals during agonist-induced insulin secretion in pancreatic β-cells

TRPM4 is a Ca2+-activated non-selective cation (CAN) channel that functions in cell depolarization, which is important for Ca2+ influx and insulin secretion in pancreatic beta-cells. We investigated TRPM4 expression and function in the P-cell lines HIT-T15 (hamster), RINm5F (rat), beta-TC3 (mouse), MIN-6 (mouse) and the alpha-cell line INR1G9 (hamster). By RT-PCR, we identified TRPM4 transcripts in alpha- and beta-cells. Patch-clamp recordings with increasing Ca2+ concentrations resulted in a dose-dependent activation of TRPM4 with the greatest depolarizing currents recorded from hamster-derived cells. Further, Ca2+ imaging experiments revealed that inhibition of TRPM4 by a dominant-negative effect significantly decreased the magnitude of the Ca2+ signals generated by agonist stimulation compared to control cells. The decrease in the [Ca2+], resulted in reduced insulin secretion. Our data suggest that depolarizing currents generated by TRPM4 are an important component in the control of intracellular Ca2+ signals necessary for insulin secretion and perhaps glucagon from alpha-cells.(c) 2008 Elsevier Ireland Ltd. All rights reserved.