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

6 Citations (Scopus)

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

Fingerprint

Islets of Langerhans
Serum
Knockout Mice
Cell Physiological Phenomena
Apoptosis
Polymerase Chain Reaction

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

Cite this

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum. / Yang, Guang; Shi, Yue; Yu, Jia; Li, Yuxin; Yu, Lina; Welling, Andrea; Hofmann, Franz; Striessnig, Jörg; Juntti-Berggren, Lisa; Berggren, Per Olof; Yang, Shao Nian.

In: Cellular and Molecular Life Sciences, Vol. 72, No. 6, 2015, p. 1197-1207.

Research output: Contribution to journalArticle

Yang, G, Shi, Y, Yu, J, Li, Y, Yu, L, Welling, A, Hofmann, F, Striessnig, J, Juntti-Berggren, L, Berggren, PO & Yang, SN 2015, 'CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum', Cellular and Molecular Life Sciences, vol. 72, no. 6, pp. 1197-1207. https://doi.org/10.1007/s00018-014-1737-6
Yang, Guang ; Shi, Yue ; Yu, Jia ; Li, Yuxin ; Yu, Lina ; Welling, Andrea ; Hofmann, Franz ; Striessnig, Jörg ; Juntti-Berggren, Lisa ; Berggren, Per Olof ; Yang, Shao Nian. / CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum. In: Cellular and Molecular Life Sciences. 2015 ; Vol. 72, No. 6. pp. 1197-1207.
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