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First published online on July 25, 2006
This version published online on September 21, 2006
Endocrine Reviews, doi:10.1210/er.2005-0888
A more recent version of this article appeared on October 1, 2006
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The Role of Voltage-Gated Calcium Channels in Pancreatic {beta}-Cell Physiology and Pathophysiology

Shao-Nian Yang* and Per-Olof Berggren*

The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: shao-nian.yang{at}ki.se or per-olof.berggren{at}ki.se.

Voltage-gated calcium (CaV) channels are ubiquitously expressed in various cell types throughout the body. In principle, the molecular identity, biophysical profile, and pharmacological property of CaV channels are independent of the cell type where they reside, whereas these channels execute unique functions in different cell types, such as muscle contraction, neurotransmitter release, and hormone secretion. At least six CaV{alpha}1 subunits, including CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1, have been identified in pancreatic {beta}-cells. These pore-forming subunits complex with certain auxiliary subunits to conduct L-, P/Q-, N-, R-, and T-type CaV currents, respectively. {beta}-Cell CaV channels take center stage in insulin secretion and play an important role in {beta}-cell physiology and pathophysiology. CaV3 channels become expressed in diabetes-prone mouse {beta}-cells. Point mutation in the human CaV1.2 gene results in excessive insulin secretion. Trinucleotide expansion in the human CaV1.3 and CaV2.1 gene is revealed in a subgroup of patients with type 2 diabetes. {beta}-Cell CaV channels are regulated by a wide range of mechanisms, either shared by other cell types or specific to {beta}-cells, to always guarantee a satisfactory concentration of Ca2+. Inappropriate regulation of {beta}-cell CaV channels causes {beta}-cell dysfunction and even death manifested in both type 1 and type 2 diabetes. This review summarizes current knowledge of CaV channels in {beta}-cell physiology and pathophysiology.




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