Accelerated inactivation of cardiac L-type calcium channels triggered by anaesthetic-induced preconditioning


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Abstract

Mandarin translation of abstractBackground and purpose:Cardioprotection against ischaemia by anaesthetic-induced preconditioning (APC) is well established. However, the mechanism underlying Ca2+ 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 Ca2+ current (ICa,L) characteristics and calmodulin (CaM) levels were determined by Western blot analysis. Cytosolic Ca2+ levels were monitored using fluo-4-AM. Action potential (AP) simulations examined the effects of APC.Key results:In Wistar rats, APC significantly accelerated ICa,L inactivation kinetics. This was abolished when external Ca2+ was replaced with Ba2+, suggesting that Ca2+-dependent inactivation of ICa,L was modulated by APC. Expression levels of CaM, a determinant of ICa,L inactivation, were not affected. Attenuation of cytosolic Ca2+ accumulation following oxidative stress was observed in the APC group. Simulations showed that the accelerated inactivation of ICa,L resulted in a shortening of the AP duration. The Dahl S rat strain was resistant to APC and changes in ICa,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 Ca2+ influx and attenuation of Ca2+ overload during ischaemia/reperfusion.

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