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• W2021892152 abstract "Diastolic depolarization (DD) of atrial myocytes can lead to spontaneous action potentials (APs) and, potentially, atrial tachyarrhythmias. This study examined the hypotheses that 1) a slowly inactivating component of the Na + current (referred to as late I Na ) may contribute to DD and initiate AP firing and that 2) blocking late I Na will reduce spontaneous and induced firing of APs by atrial myocytes. Guinea pig atrial myocytes without or with DD and spontaneous AP firing were studied using the whole cell patch-clamp technique. In experiments using cells with a stable resting membrane potential (no spontaneous DD or firing), hydrogen peroxide (H 2 O 2 , 50 μmol/l) caused DD and AP firing. The H 2 O 2 -induced activity was suppressed by the late I Na inhibitors tetrodotoxin (TTX, 1 μmol/l) and ranolazine (5 μmol/l). In cells with DD but no spontaneous APs, the late I Na enhancer anemone toxin II (ATX-II, 10 nmol/l) accelerated DD and induced APs. In cells with DD and spontaneous AP firing, TTX and ranolazine (both, 1 μmol/l) significantly reduced the slope of DD by 81 ± 12% and 75 ± 11% and the frequency of spontaneous firing by 70 ± 15% and 74 ± 9%, respectively. Ramp voltage-clamp simulating DD elicited a slow inward current. TTX at 1, 3, and 10 μmol/l inhibited this current by 41 ± 4%, 73 ± 2%, and 91 ± 1%, respectively, suggesting that a slowly inactivating I Na underlies the DD. ATX-II and H 2 O 2 increased the amplitude of this current, and the effects of ATX-II and H 2 O 2 were attenuated by ranolazine or TTX. In conclusion, late I Na can contribute to the DD of atrial myocytes and the inhibition of this current suppresses atrial DD and spontaneous APs." @default.
• W2021892152 created "2016-06-24" @default.
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• W2021892152 date "2009-10-01" @default.
• W2021892152 modified "2023-10-18" @default.
• W2021892152 title "A slowly inactivating sodium current contributes to spontaneous diastolic depolarization of atrial myocytes" @default.
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• W2021892152 doi "https://doi.org/10.1152/ajpheart.00444.2009" @default.
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