1. Ca1.2 and Ca1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum.
- Author
-
Yang, Guang, Shi, Yue, Yu, Jia, Li, Yuxin, Yu, Lina, Welling, Andrea, Hofmann, Franz, Striessnig, Jörg, Juntti-Berggren, Lisa, Berggren, Per-Olof, and Yang, Shao-Nian
- Subjects
- *
ISLANDS of Langerhans , *DIABETES , *SERUM , *APOPTOSIS , *PANCREATIC beta cells , *LABORATORY mice - Abstract
The voltage-gated Ca (Ca) channel acts as a key player in β cell physiology and pathophysiology. β cell Ca channels undergo hyperactivation subsequent to exposure to type 1 diabetic (T1D) serum resulting in increased cytosolic free Ca concentration and thereby Ca-triggered β cell apoptosis. The present study was aimed at revealing the subtypes of Ca1 channels hyperactivated by T1D serum as well as the biophysical mechanisms responsible for T1D serum-induced hyperactivation of β cell Ca1 channels. Patch-clamp recordings and single-cell RT-PCR analysis were performed in pancreatic β cells from Ca1 channel knockout and corresponding control mice. We now show that functional Ca1.3 channels are expressed in a subgroup of islet β cells from Ca1.2 knockout mice (Ca1.2). T1D serum enhanced whole-cell Ca currents in islet β cells from Ca1.3 knockout mice (Ca1.3). T1D serum increased the open probability and number of functional unitary Ca1 channels in Ca1.2 and Ca1.3 β cells. These data demonstrate that T1D serum hyperactivates both Ca1.2 and Ca1.3 channels by increasing their conductivity and number. These findings suggest Ca1.2 and Ca1.3 channels as potential targets for anti-diabetes therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF