Inhibition of reverse Na+/Ca2+ exchange with KB-R7943 alters contractility in autumn but not summer ground squirrel myocardium, suggesting a role in pre-hibernation calcium homeostasis remodeling.
KB-R7943 effects on contractility differ seasonally in squirrel myocardium; leaves open NCX role in hibernator adaptation and any human relevance.
We investigated the effect of KB-R7943, an inhibitor of the reverse mode of Na + /Ca 2+ exchanger, on the force of isometric contractions, the contractile force–frequency relationship and post-rest potentiation (a qualitative parameter of Ca 2+ levels in sarcoplasmic reticulum) in the right ventricle papillary muscles isolated from ground squirrel hearts during summer (June, n = 4) and autumn (October, n = 4) activities. In the presence of 1.8 mM Ca2+at 36°C, 1–1.5 hours-long treatment of the summer papillary muscles with KB-R7943 produced no significant effects on the contractile indices at the majority of stimulation frequencies. In the autumn papillary muscles KB-R7943 induced a 40–50% decrease in the force of contraction (negative inotropic effect) at low stimulation frequencies (0.1–0.3 Hz) without any significant effect at higher stimulation frequencies (0.4–3.0 Hz). Furthermore, in this group, KB-R7943 suppressed the post-rest potentiation of contractility by 50 ± 21% at pause durations exceeding 120 s. These observations indicate that KB-R7943 can affect Ca 2+ levels in sarcoplasmic reticulum and that Na + /Ca2 + exchange may contribute to the physiological remodeling of intracellular Ca 2+ homeostasis in myocardium of hibernating animals prior their transition to a hypometabolic torpid state.
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Аверин et al. (2017) studied this question.
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