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 Berggren, Shao Nian Yang

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1197-1207
Number of pages11
JournalCellular and Molecular Life Sciences
Volume72
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

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    Yang, G., Shi, Y., Yu, J., Li, Y., Yu, L., Welling, A., Hofmann, F., Striessnig, J., Juntti-Berggren, L., Berggren, P. O., & Yang, S. N. (2015). CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum. Cellular and Molecular Life Sciences, 72(6), 1197-1207. https://doi.org/10.1007/s00018-014-1737-6