T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting beta-cell line, INS-1

被引:55
作者
Bhattacharjee, A
Whitehurst, RM
Zhang, M
Wang, L
Li, M
机构
[1] UNIV S ALABAMA, COLL MED, DEPT PHARMACOL, MOBILE, AL 36688 USA
[2] UNIV S ALABAMA, COLL MED, DEPT PEDIAT, MOBILE, AL 36688 USA
关键词
D O I
10.1210/en.138.9.3735
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The present study addresses the function of T-type voltage-gated calcium channels in insulin-secreting cells. We used whole-cell voltage and current recordings, capacitance measurements, and RIA techniques to determine the contribution of T-type calcium channels in modulation of electrical activity and in stimulus-secretion coupling in a rat insulin secreting cell line, INS-1. By employing a double pulse protocol in the current-clamp mode, we found that activation of T-type calcium channels provided a low threshold depolarizing potential that decreased the latency of onset of action potentials and furthermore increased the frequency of action potentials, both of which are abolished by administration of nickel chloride (NiCl2), a selective T-type calcium channel blocker. Moreover application of high frequency stimulation, as compared with low frequency stimulation, caused a greater change in membrane capacitance (Delta Cm), suggesting higher insulin secretion. We demonstrated that glucose stimulated insulin secretion in INS-1 is reduced 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 hyperinsulinemia, the T-type calcium channel may be a therapeutic target.
引用
收藏
页码:3735 / 3740
页数:6
相关论文
共 41 条
[1]   Adrenaline, not somatostatin-induced hyperpolarization is accompanied by a sustained inhibition of insulin secretion in INS-1 cells. Activation of sulphonylurea K-ATP(+) channels is not involved [J].
Abel, KB ;
Lehr, S ;
Ullrich, S .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1996, 432 (01) :89-96
[2]   EXOCYTOSIS ELICITED BY ACTION-POTENTIALS AND VOLTAGE-CLAMP CALCIUM CURRENTS IN INDIVIDUAL MOUSE PANCREATIC B-CELLS [J].
AMMALA, C ;
ELIASSON, L ;
BOKVIST, K ;
LARSSON, O ;
ASHCROFT, FM ;
RORSMAN, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1993, 472 :665-688
[3]   ESTABLISHMENT OF 2-MERCAPTOETHANOL-DEPENDENT DIFFERENTIATED INSULIN-SECRETING CELL-LINES [J].
ASFARI, M ;
JANJIC, D ;
MEDA, P ;
LI, GD ;
HALBAN, PA ;
WOLLHEIM, CB .
ENDOCRINOLOGY, 1992, 130 (01) :167-178
[4]  
ASHCROFT FM, 1989, DIABETOLOGIA, V32, P591
[5]   2 TYPES OF CA CHANNEL IN RAT PANCREATIC BETA-CELLS [J].
ASHCROFT, FM ;
KELLY, RP ;
SMITH, PA .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1990, 415 (04) :504-506
[6]   ELECTROPHYSIOLOGY OF THE PANCREATIC BETA-CELL [J].
ASHCROFT, FM ;
RORSMAN, P .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1989, 54 (02) :87-143
[7]   Voltage dependent Na+ and Ca2+ currents in human pancreatic islet beta-cells: Evidence for roles in the generation of action potentials and insulin secretion [J].
Barnett, DW ;
Pressel, DM ;
Misler, S .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1995, 431 (02) :272-282
[8]   VOLTAGE-GATED CALCIUM CURRENTS HAVE 2 OPPOSING EFFECTS ON THE SECRETION OF ALDOSTERONE [J].
BARRETT, PQ ;
ERTEL, EA ;
SMITH, MM ;
NEE, JJ ;
COHEN, CJ .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 268 (04) :C985-C992
[9]   2 KINDS OF CALCIUM CHANNELS IN CANINE ATRIAL CELLS - DIFFERENCES IN KINETICS, SELECTIVITY AND PHARMACOLOGY [J].
BEAN, BP .
JOURNAL OF GENERAL PHYSIOLOGY, 1985, 86 (01) :1-30
[10]   CA2+ AND PANCREATIC B-CELL FUNCTION [J].
BERGGREN, PO ;
LARSSON, O .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1994, 22 (01) :12-18