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Accelerated inactivation of cardiac L‐type calcium channels triggered by anaesthetic‐induced preconditioning
Author(s) -
Tampo A,
Hogan CS,
Sedlic F,
Bosnjak ZJ,
Kwok WM
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2008.00026.x
Subject(s) - isoflurane , chemistry , calcium , l type calcium channel , patch clamp , voltage dependent calcium channel , pharmacology , medicine , biochemistry , receptor , organic chemistry
Mandarin translation of abstract Background and purpose: Cardioprotection against ischaemia by anaesthetic‐induced preconditioning (APC) is well established. However, the mechanism underlying Ca 2+ overload attenuation by APC is unknown. The effects of APC by isoflurane on the cardiac L‐type Ca channel were investigated. Experimental approach: In a model of in vivo APC, Wistar rats were exposed to isoflurane (1.4%), delivered via a vaporizer in an enclosure, prior to thoracotomy. The Dahl S rats were similarly preconditioned to determine strain‐dependent effects. Whole‐cell patch clamp using cardiac ventricular myocytes was used to determine the L‐type Ca 2+ current (I Ca,L ) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca 2+ levels were monitored using fluo‐4‐AM. Action potential (AP) simulations examined the effects of APC. Key results: In Wistar rats, APC significantly accelerated I Ca,L inactivation kinetics. This was abolished when external Ca 2+ was replaced with Ba 2+ , suggesting that Ca 2+ ‐dependent inactivation of I Ca,L was modulated by APC. Expression levels of CaM, a determinant of I Ca,L inactivation, were not affected. Attenuation of cytosolic Ca 2+ accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of I Ca,L resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in I Ca,L inactivation were not observed in cardiomyocytes prepared from these rats. Conclusions and implications: APC triggered persistent changes in the inactivation of cardiac L‐type Ca channels. This can potentially lead to a reduction in Ca 2+ influx and attenuation of Ca 2+ overload during ischaemia/reperfusion. Mandarin translation of abstract