| RRC ID |
21269
|
| Author |
Tian X, Zhou Y, Gao L, He G, Jiang W, Li W, Takahashi E.
|
| Title |
Analysis of ischemic neuronal injury in Cav2.1 channel α1 subunit mutant mice.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
One of the main instigators leading to cell death and brain damage following ischemia is Ca(2+) dysregulation. Neuronal membrane depolarization results in the activation of voltage-gated Ca(2+) (CaV) channels and intracellular Ca(2+) influx. We investigated the physiological role of the CaV2.1 (P/Q-type) channel in ischemic neuronal injury using CaV2.1 channel α1 subunit mutant mice, rolling Nagoya and leaner mice. The in vivo ischemia model with a complete occlusion of the middle cerebral artery showed that the infarct area at 24h was significantly smaller in rolling Nagoya (27.1±3.5% of total brain volume) and leaner (20.1±3.5%) mice compared to wild-type (42.9±4.5%) mice. In an in vitro Ca(2+) imaging study, oxygen-glucose deprivation using a hippocampal slice induced a significantly slower rate of increase in intracellular Ca(2+) concentration ([Ca(2+)]i) in rolling Nagoya (0.083±0.007/min) and leaner (0.062±0.006/min) mice compared to wild-type (0.105±0.008/min) mice. These results demonstrate that the mutant CaV2.1 channel in rolling Nagoya and leaner mice plays a different protective role in a ([Ca(2+)]i)-dependent manner in ischemic models and indicate that CaV2.1 channel blockers may be used preventively against ischemic injury.
|
| Volume |
434(1)
|
| Pages |
60-4
|
| Published |
2013-4-26
|
| DOI |
10.1016/j.bbrc.2013.03.066
|
| PII |
S0006-291X(13)00520-2
|
| PMID |
23545255
|
| MeSH |
Animals
Brain Ischemia / genetics
Brain Ischemia / pathology*
Brain Ischemia / physiopathology*
Calcium Channel Blockers / pharmacology
Calcium Channels, N-Type / genetics*
Calcium Channels, N-Type / physiology
Disease Models, Animal
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Neurons / drug effects
Neurons / pathology
Protein Subunits / genetics
Protein Subunits / physiology
|
| IF |
2.985
|
| Times Cited |
9
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Mice |
RBRC00388 |
