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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | García, Mc Carrillo, Ed Hernández, A. Zaldívar, D. Sánchez, Ja González, G. |
| Description | Author Affiliation: González G ( Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del I.P.N. México, México.) |
| Abstract | BACKGROUND AND PURPOSE: Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K(+) (mitoK(ATP) ) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca(2+) homeostasis during PPC, particularly changes in Ca(2+) channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca(2+) channels. EXPERIMENTAL APPROACH: PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca(2+) signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the (1c) subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTS: PPC was accompanied by a 50% reduction in (1c) subunit levels, and by a reversible fall in L-type current amplitude and Ca(2+) transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoK(ATP) channel blocker 5-hydroxydecanoate (5-HD). PPC significantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the (1c) subunit and Ca(2+) channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONS: PPC downregulated the (1c) subunit, possibly through ROS. Downregulation involved increased degradation of the Ca(2+) channel, which in turn reduced Ca(2+) influx, which may attenuate Ca(2+) overload during reperfusion. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 161 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2010-11-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Calcium Channels, L-Type Drug Effects Diazoxide Pharmacology Down-Regulation Ischemic Preconditioning, Myocardial Action Potentials Animals Blotting, Western Metabolism Calcium Signaling Myocardial Infarction Prevention & Control Myocardial Reperfusion Injury Physiopathology Myocytes, Cardiac Patch-Clamp Techniques Potassium Channels Rats, Wistar Reactive Oxygen Species Vasodilator Agents Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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