caa a22 4500 606175059 CHVBK 20210128100741.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s00018-014-1737-6 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1737-6 CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum [Elektronische Daten] [Guang Yang, Yue Shi, Jia Yu, Yuxin Li, Lina Yu, Andrea Welling, Franz Hofmann, Jörg Striessnig, Lisa Juntti-Berggren, Per-Olof Berggren, Shao-Nian Yang] The voltage-gated Ca2+ (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 Ca2+ concentration and thereby Ca2+-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. Springer Basel, 2014 Apolipoprotein nationallicence Calcium channel nationallicence Genetic ablation nationallicence Patch-clamp recording nationallicence Single-cell RT-PCR nationallicence Type 1 diabetes nationallicence CaV : Voltage-gated calcium nationallicence CaV1.2−/− : CaV1.2 subunit knockout nationallicence CaV1.3−/− : CaV1.3 subunit knockout nationallicence DHP : Dihydropyridine nationallicence T1D : Type 1 diabetic nationallicence Yang Guang The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Shi Yue The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Yu Jia The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Li Yuxin National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, 130024, Changchun, China aut Yu Lina The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Welling Andrea Forschergruppe, Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802, München, Germany aut Hofmann Franz Forschergruppe, Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802, München, Germany aut Striessnig Jörg Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020, Innsbruck, Austria aut Juntti-Berggren Lisa The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Berggren Per-Olof The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Yang Shao-Nian The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut Cellular and Molecular Life Sciences Springer Basel 72/6(2015-03-01), 1197-1207 1420-682X 72:6<1197 2015 72 18 https://doi.org/10.1007/s00018-014-1737-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1737-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Guang The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Shi Yue The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Yu Jia The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Li Yuxin National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, 130024, Changchun, China aut NATIONALLICENCE 700 1- Yu Lina The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Welling Andrea Forschergruppe, Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802, München, Germany aut NATIONALLICENCE 700 1- Hofmann Franz Forschergruppe, Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802, München, Germany aut NATIONALLICENCE 700 1- Striessnig Jörg Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020, Innsbruck, Austria aut NATIONALLICENCE 700 1- Juntti-Berggren Lisa The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Berggren Per-Olof The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 700 1- Yang Shao-Nian The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, 171 76, Stockholm, Sweden aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/6(2015-03-01), 1197-1207 1420-682X 72:6<1197 2015 72 18