The Role of Voltage-Gated Calcium Channels in Pancreatic ß-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
Correspondence: Address all correspondence and requests for reprints to: Shao-Nian Yang, Ph.D., or Per-Olof Berggren, Ph.D., The Rolf Luft Research Center for Diabetes and Endocrinology L1:03, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. E-mail: shao-nian.yang{at}ki.se or per-olof.berggren{at}ki.se
Voltage-gated calcium (CaV) channels are ubiquitously expressedin various cell types throughout the body. In principle, themolecular identity, biophysical profile, and pharmacologicalproperty of CaV channels are independent of the cell type wherethey reside, whereas these channels execute unique functionsin different cell types, such as muscle contraction, neurotransmitterrelease, and hormone secretion. At least six CaV1 subunits,including CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1,have been identified in pancreatic ß-cells. Thesepore-forming subunits complex with certain auxiliary subunitsto conduct L-, P/Q-, N-, R-, and T-type CaV currents, respectively.ß-Cell CaV channels take center stage in insulin secretionand play an important role in ß-cell physiology andpathophysiology. CaV3 channels become expressed in diabetes-pronemouse ß-cells. Point mutation in the human CaV1.2gene results in excessive insulin secretion. Trinucleotide expansionin the human CaV1.3 and CaV2.1 gene is revealed in a subgroupof patients with type 2 diabetes. ß-Cell CaV channelsare regulated by a wide range of mechanisms, either shared byother cell types or specific to ß-cells, to alwaysguarantee a satisfactory concentration of Ca2+. Inappropriateregulation of ß-cell CaV channels causes ß-celldysfunction and even death manifested in both type 1 and type2 diabetes. This review summarizes current knowledge of CaVchannels in ß-cell physiology and pathophysiology.
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1 subunits, including CaV1.2, CaV1.3, CaV2.1, CaV2.2, CaV2.3, and CaV3.1, have been identified in pancreatic ß-cells. These pore-forming subunits complex with certain auxiliary subunits to conduct L-, P/Q-, N-, R-, and T-type CaV currents, respectively. ß-Cell CaV channels take center stage in insulin secretion and play an important role in ß-cell physiology and pathophysiology. CaV3 channels become expressed in diabetes-prone mouse ß-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. ß-Cell CaV channels are regulated by a wide range of mechanisms, either shared by other cell types or specific to ß-cells, to always guarantee a satisfactory concentration of Ca2+. Inappropriate regulation of ß-cell CaV channels causes ß-cell dysfunction and even death manifested in both type 1 and type 2 diabetes. This review summarizes current knowledge of CaV channels in ß-cell physiology and pathophysiology. 
