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Cellular and Molecular Life Sciences

, Volume 72, Issue 6, pp 1197–1207 | Cite as

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum

  • Guang Yang
  • Yue Shi
  • Jia Yu
  • Yuxin Li
  • Lina Yu
  • Andrea Welling
  • Franz Hofmann
  • Jörg Striessnig
  • Lisa Juntti-Berggren
  • Per-Olof BerggrenEmail author
  • Shao-Nian YangEmail author
Research Article

Abstract

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.

Keywords

Apolipoprotein Calcium channel Genetic ablation Patch-clamp recording Single-cell RT-PCR Type 1 diabetes 

Abbreviations

CaV

Voltage-gated calcium

CaV1.2−/−

CaV1.2 subunit knockout

CaV1.3−/−

CaV1.3 subunit knockout

DHP

Dihydropyridine

T1D

Type 1 diabetic

Notes

Acknowledgments

This work was supported by grants from Berth von Kantzow’s Foundation, Diabetes Research and Wellness Foundation, EuroDia (FP6-518153), European Research Council (ERC-2013-AdG), the Family Erling-Persson Foundation, Funds of Karolinska Institutet, the Knut and Alice Wallenberg Foundation, Skandia Insurance Company, Ltd., the Stichting af Jochnick Foundation, Strategic Research Program in Diabetes at Karolinska Institutet, the Swedish Diabetes Association, the Swedish Research Council and the Novo Nordisk Foundation. P-OB is the founder of the Biotech Company BioCrine AB and is also a member of the board of this company. S-NY is a consultant to BioCrine AB. Biocrine AB is pursuing ApoCIII as a novel druggable target in diabetes.

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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Guang Yang
    • 1
    • 2
  • Yue Shi
    • 1
  • Jia Yu
    • 1
  • Yuxin Li
    • 3
  • Lina Yu
    • 1
  • Andrea Welling
    • 4
  • Franz Hofmann
    • 4
  • Jörg Striessnig
    • 5
  • Lisa Juntti-Berggren
    • 1
  • Per-Olof Berggren
    • 1
    Email author
  • Shao-Nian Yang
    • 1
    • 3
    Email author
  1. 1.The Rolf Luft Research Center for Diabetes and EndocrinologyKarolinska InstitutetStockholmSweden
  2. 2.Jilin Academy of Traditional Chinese MedicineChangchunChina
  3. 3.National Engineering Laboratory for Druggable Gene and Protein ScreeningNortheast Normal UniversityChangchunChina
  4. 4.Forschergruppe, Institut für Pharmakologie und ToxikologieTechnische Universität MünchenMünchenGermany
  5. 5.Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular BiosciencesUniversity of InnsbruckInnsbruckAustria

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