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• W2146395354 abstract "Phospholemman (PLM), when phosphorylated at serine 68, relieves its inhibition on Na + -K + -ATPase but inhibits Na + /Ca 2+ exchanger 1 (NCX1) in cardiac myocytes. Under stress when catecholamine levels are high, enhanced Na + -K + -ATPase activity by phosphorylated PLM attenuates intracellular Na + concentration ([Na + ] i ) overload. To evaluate the effects of PLM on NCX1 on in vivo cardiac contractility, we injected recombinant adeno-associated virus (serotype 9) expressing either the phosphomimetic PLM S68E mutant or green fluorescent protein (GFP) directly into left ventricles (LVs) of PLM-knockout (KO) mice. Five weeks after virus injection, ∼40% of isolated LV myocytes exhibited GFP fluorescence. Expression of S68E mutant was confirmed with PLM antibody. There were no differences in protein levels of α 1 - and α 2 -subunits of Na + -K + -ATPase, NCX1, and sarco(endo)plasmic reticulum Ca 2+ -ATPase between KO-GFP and KO-S68E LV homogenates. Compared with KO-GFP myocytes, Na + /Ca 2+ exchange current was suppressed, but resting [Na + ] i , Na + -K + -ATPase current, and action potential amplitudes were similar in KO-S68E myocytes. Resting membrane potential was slightly lower and action potential duration at 90% repolarization (APD 90 ) was shortened in KO-S68E myocytes. Isoproterenol (Iso; 1 μM) increased APD 90 in both groups of myocytes. After Iso, [Na + ] i increased monotonically in paced (2 Hz) KO-GFP but reached a plateau in KO-S68E myocytes. Both systolic and diastolic [Ca 2+ ] i were higher in Iso-stimulated KO-S68E myocytes paced at 2 Hz. Echocardiography demonstrated similar resting heart rate, ejection fraction, and LV mass between KO-GFP and KO-S68E mice. In vivo closed-chest catheterization demonstrated enhanced contractility in KO-S68E compared with KO-GFP hearts stimulated with Iso. We conclude that under catecholamine stress when [Na + ] i is high, PLM minimizes [Na + ] i overload by relieving its inhibition of Na + -K + -ATPase and preserves inotropy by simultaneously inhibiting Na + /Ca 2+ exchanger." @default.
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• W2146395354 date "2011-03-01" @default.
• W2146395354 modified "2023-09-29" @default.
• W2146395354 title "Regulation of in vivo cardiac contractility by phospholemman: role of Na⁺/Ca²⁺exchange" @default.
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• W2146395354 doi "https://doi.org/10.1152/ajpheart.00894.2010" @default.
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