T-TYPE CALCIUM CHANNELS FACILITATE INSULIN-SECRETION BY ENHANCING GENERAL EXCITABILITY IN THE INSULIN-SECRETING BETA-CELL LINE, INS-1

The present study addresses the function of T-type voltage-gated calci um channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to d etermine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insuli n secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium cha nnels provided a low threshold depolarizing potential that decreased t he latency of onset of action potentials and furthermore increased the frequency of action potentials, both of which are abolished by admini stration of nickel chloride (NiCl2), a selective T-type calcium channe l blocker. Moreover application of high frequency stimulation, as comp ared with low frequency stimulation, caused a greater change in membra ne capacitance (Delta Cm), suggesting higher insulin secretion. We dem onstrated that glucose stimulated insulin secretion in INS-1 is reduce d dose dependently by NiCl2. We conclude that T-type calcium channels facilitate insulin secretion by enhancing the general excitability of these cells. In light of the pathological effects of both hypo and hyp erinsulinemia, the T-type calcium channel may be a therapeutic target.