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) |
|---|---|
| Pages (from-to) | 1197-1207 |
| Number of pages | 11 |
| Journal | Cellular and Molecular Life Sciences |
| Volume | 72 |
| Issue number | 6 |
| DOIs | |
| State | Published - 2015 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum
AU - Yang, Guang
AU - Shi, Yue
AU - Yu, Jia
AU - Li, Yuxin
AU - Yu, Lina
AU - Welling, Andrea
AU - Hofmann, Franz
AU - Striessnig, Jörg
AU - Juntti-Berggren, Lisa
AU - Berggren, Per Olof
AU - Yang, Shao Nian
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Apolipoprotein
KW - Calcium channel
KW - Genetic ablation
KW - Patch-clamp recording
KW - Single-cell RT-PCR
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84925539468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925539468&partnerID=8YFLogxK
U2 - 10.1007/s00018-014-1737-6
DO - 10.1007/s00018-014-1737-6
M3 - Article
C2 - 25292336
AN - SCOPUS:84925539468
VL - 72
SP - 1197
EP - 1207
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 6
ER -