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- W4311852593 endingPage "1239" @default.
- W4311852593 startingPage "1239" @default.
- W4311852593 abstract "Various models, including stem cells derived and isolated cardiomyocytes with overexpressed channels, are utilized to analyze the functional interplay of diverse ion currents involved in cardiac automaticity and excitation–contraction coupling control. Here, we used β-NAD and ammonia, known hyperpolarizing and depolarizing agents, respectively, and applied inhibitory analysis to reveal the interplay of several ion channels implicated in rat papillary muscle contractility control. We demonstrated that: 4 mM β-NAD, having no strong impact on resting membrane potential (RMP) and action potential duration (APD90) of ventricular cardiomyocytes, evoked significant suppression of isometric force (F) of paced papillary muscle. Reactive blue 2 restored F to control values, suggesting the involvement of P2Y-receptor-dependent signaling in β-NAD effects. Meantime, 5 mM NH4Cl did not show any effect on F of papillary muscle but resulted in significant RMP depolarization, APD90 shortening, and a rightward shift of I–V relationship for total steady state currents in cardiomyocytes. Paradoxically, NH4Cl, being added after β-NAD and having no effect on RMP, APD, and I–V curve, recovered F to the control values, indicating β-NAD/ammonia antagonism. Blocking of HCN, Kir2.x, and L-type calcium channels, Ca2+-activated K+ channels (SK, IK, and BK), or NCX exchanger reverse mode prevented this effect, indicating consistent cooperation of all currents mediated by these channels and NCX. We suggest that the activation of Kir2.x and HCN channels by extracellular K+, that creates positive and negative feedback, and known ammonia and K+ resemblance, may provide conditions required for the activation of all the chain of channels involved in the interplay. Here, we present a mechanistic model describing an interplay of channels and second messengers, which may explain discovered antagonism of β-NAD and ammonia on rat papillary muscle contractile activity." @default.
- W4311852593 created "2023-01-01" @default.
- W4311852593 creator A5005303959 @default.
- W4311852593 creator A5054457539 @default.
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- W4311852593 creator A5067617356 @default.
- W4311852593 creator A5070232549 @default.
- W4311852593 creator A5072378868 @default.
- W4311852593 creator A5077478518 @default.
- W4311852593 date "2022-12-07" @default.
- W4311852593 modified "2023-09-27" @default.
- W4311852593 title "Regulation of Papillary Muscle Contractility by NAD and Ammonia Interplay: Contribution of Ion Channels and Exchangers" @default.
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