Store-operated Ca2 entry supports contractile function in hearts of hibernatorsReport as inadecuate

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Hibernators have a distinctive ability to adapt to seasonal changes of body temperature in a range between 37°C and near freezing, exhibiting, among other features, a unique reversibility of cardiac contractility. The adaptation of myocardial contractility in hibernation state relies on alterations of excitation contraction coupling, which becomes less-dependent from extracellular Ca2+ entry and is predominantly controlled by Ca2+ release from sarcoplasmic reticulum, replenished by the Ca2+-ATPase SERCA. We found that the specific SERCA inhibitor cyclopiazonic acid CPA, in contrast to its effect in papillary muscles PM from rat hearts, did not reduce but rather potentiated contractility of PM from hibernating ground squirrels GS. In GS ventricles we identified drastically elevated, compared to rats, expression of Orai1, Stim1 and Trpc1-3-4-5-6-7 mRNAs, putative components of store operated Ca2+ channels SOC. Trpc3 protein levels were found increased in winter compared to summer GS, yet levels of Trpc5, Trpc6 or Trpc7 remained unchanged. Under suppressed voltage-dependent K+, Na+ and Ca2+ currents, the SOC inhibitor 2-aminoethyl diphenylborinate 2-APB diminished whole-cell membrane currents in isolated cardiomyocytes from hibernating GS, but not from rats. During cooling-reheating cycles 30°C–7°C–30°C of ground squirrel PM, 2-APB did not affect typical CPA-sensitive elevation of contractile force at low temperatures, but precluded the contractility at 30°C before and after the cooling. Wash-out of 2-APB reversed PM contractility to control values. Thus, we suggest that SOC play a pivotal role in governing the ability of hibernator hearts to maintain their function during the transition in and out of hibernating states.

Author: Olga V. Nakipova, Alexey S. Averin, Edward V. Evdokimovskii, Oleg Yu. Pimenov, Leonid Kosarski, Dmitriy Ignat’ev, Andrey Anufri



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