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• W1967084145 abstract "Background Recent experiments in atrial myocytes indicate that withdrawal of cholinergic agonist can directly increase Ca 2+ influx via L-type Ca 2+ current and stimulate Ca 2+ uptake into the sarcoplasmic reticulum (SR), thereby increasing intracellular Ca 2+ . Overload of cellular Ca 2+ within the SR can initiate various types of atrial dysrhythmias. The present study was designed to determine whether withdrawal of acetylcholine (ACh) can elicit Ca 2+ -induced delayed afterdepolarizations (DADs) in atrial myocytes. Methods and Results A nystatin perforated-patch whole-cell method and fluorescence microscopy (indo 1) were used to measure electrical activities and intracellular free Ca 2+ ([Ca 2+ ] i ), respectively. Withdrawal of ACh (1 μmol/L) increased action potential duration, shifted plateau voltage toward positive, and generated DADs that initiated spontaneous action potentials. Voltage-clamp analysis revealed that withdrawal of ACh elicited a rebound stimulation of L-type Ca 2+ current ( I Ca,L ) (+45%) and Na/Ca exchange current ( I NaCa ) (+16%) and the appearance of transient inward current ( I ti ) and spontaneous [Ca 2+ ] i transients. Each of these changes induced by withdrawal of ACh was abolished by Rp-cAMPs (50 to 100 μmol/L) or H-89 (2 μmol/L), inhibitors of cAMP-dependent protein kinase A. Ryanodine (1 μmol/L) abolished I NaCa and the appearance of I ti without decreasing the rebound stimulation of I Ca,L elicited by withdrawal of ACh. Conclusions Withdrawal of ACh can elicit cAMP-mediated stimulation of Ca 2+ influx via I Ca,L and uptake of SR Ca 2+ . As a result, cellular Ca 2+ overload causes enhanced SR Ca 2+ release and the initiation of DADs. These mechanisms may generate triggered and/or spontaneous atrial depolarizations elicited by withdrawal of vagal nerve activity." @default.
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• W1967084145 date "1997-08-19" @default.
• W1967084145 modified "2023-10-18" @default.
• W1967084145 title "Withdrawal of Acetylcholine Elicits Ca ²⁺ -Induced Delayed Afterdepolarizations in Cat Atrial Myocytes" @default.
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• W1967084145 doi "https://doi.org/10.1161/01.cir.96.4.1275" @default.
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