The role of voltage-gated calcium channels in pancreatic beta-cell physiology and pathophysiology.
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 CaValpha1 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.
Yang
Shao-Nian
SN
The Rolf Luft Research Center for Diabetes and Endocrinology L1:03, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. shao-nian.yang@ki.se
Berggren
Per-Olof
PO
D017398:Alternative Splicing; D000818:Animals; D015220:Calcium Channels / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D017434:Protein Structure, Tertiary
D015220:Calcium Channels