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 language | English (US) |
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Pages (from-to) | 1197-1207 |
Number of pages | 11 |
Journal | Cellular and Molecular Life Sciences |
Volume | 72 |
Issue number | 6 |
DOIs | |
State | Published - Mar 2015 |
Externally published | Yes |
Keywords
- Apolipoprotein
- Calcium channel
- Genetic ablation
- Patch-clamp recording
- Single-cell RT-PCR
- Type 1 diabetes
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Cellular and Molecular Neuroscience
- Cell Biology