title: CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum.
abstract: The voltage-gated Ca(2+) (CaV) channel acts as a key player in β cell physiology and pathophysiology. β cell CaV channels undergo hyperactivation subsequent to exposure to type 1 diabetic (T1D) serum resulting in increased cytosolic free Ca(2+) concentration and thereby Ca(2+)-triggered β cell apoptosis. The present study was aimed at revealing the subtypes of CaV1 channels hyperactivated by T1D serum as well as the biophysical mechanisms responsible for T1D serum-induced hyperactivation of β cell CaV1 channels. Patch-clamp recordings and single-cell RT-PCR analysis were performed in pancreatic β cells from CaV1 channel knockout and corresponding control mice. We now show that functional CaV1.3 channels are expressed in a subgroup of islet β cells from CaV1.2 knockout mice (CaV1.2(-/-)). T1D serum enhanced whole-cell CaV currents in islet β cells from CaV1.3 knockout mice (CaV1.3(-/-)). T1D serum increased the open probability and number of functional unitary CaV1 channels in CaV1.2(-/-) and CaV1.3(-/-) β cells. These data demonstrate that T1D serum hyperactivates both CaV1.2 and CaV1.3 channels by increasing their conductivity and number. These findings suggest CaV1.2 and CaV1.3 channels as potential targets for anti-diabetes therapy.
authors.affiliation: The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yue
authors.initials: Y
authors.lastname: Shi
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.forename: Andrea
authors.initials: A
authors.lastname: Welling
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Striessnig
authors.forename: Lisa
authors.initials: L
authors.lastname: Juntti-Berggren
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.forename: Shao-Nian
authors.initials: SN
authors.lastname: Yang
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005260:Female; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: C514350:CACNA1C protein, mouse; C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type