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

Background 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 (I_Ca,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 I_Ca,L inactivation kinetics. This was abolished when external Ca²⁺ was replaced with Ba²⁺, suggesting that Ca²⁺‐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 Ca²⁺ 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 Ca²⁺ influx and attenuation of Ca²⁺ overload during ischaemia/reperfusion.

Mandarin translation of abstract

DOI: 10.1111/j.1476-5381.2008.00026.x

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