Browsing by Subject "SK channels"

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    SK channels and ventricular arrhythmias in heart failure
    (Elsevier, 2015-08) Chang, Po-Cheng; Chen, Peng-Sheng; Department of Medicine, IU School of Medicine
    Small-conductance Ca2+-activated K+ (SK) currents are important in the repolarization of normal atrial (but not ventricular) cardiomyocytes. However, recent studies showed that the SK currents are upregulated in failing ventricular cardiomyocytes, along with increased SK channel protein expression and enhanced sensitivity to intracellular Ca2+. The SK channel activation may be either antiarrhythmic or proarrhythmic, depending on the underlying clinical situations. While the SK channel is a new target of antiarrhythmic therapy, drug safety is still one of the major concerns.
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    Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells
    (Elsevier, 2016-07) Tsai, Wei-Chung; Chan, Yi-Hsin; Hsueh, Chia-Hsiang; Everett, Thomas H., IV; Chang, Po-Cheng; Choi, Eue-Keun; Olaopa, Michael A.; Lin, Shien-Fong; Shen, Changyu; Kudela, Maria Aleksandra; Rubart-von der Lohe, Michael; Chen, Zhenhui; Jadiya, Pooja; Tomar, Dhanendra; Luvison, Emily; Anzalone, Nicholas; Anzalone, Nicholas; Patel, Vickas V.; Chen, Peng-Sheng; Medicine, School of Medicine
    BACKGROUND: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca(2+) in melanocytes. Homozygous Dct knockout (Dct(-/-)) adult mice are vulnerable to atrial arrhythmias (AA). OBJECTIVE: The purpose of this study was to determine whether apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) currents are upregulated in Dct(-/-) mice and contribute to AA. METHODS: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct(-/-) (n = 9) and Dct(+/-) (n = 9) mice. RESULTS: Apamin prolonged action potential duration (APD) by 18.8 ms (95% confidence interval [CI] 13.4-24.1 ms) in Dct(-/-) mice and by 11.5 ms (95% CI 5.4-17.6 ms) in Dct(+/-) mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95% CI 34-62 ms) for Dct(-/-) mice and 21 ms (95% CI 12-29 ms) for Dct(+/-) mice (P = .002) at baseline, and it was 35 ms (95% CI 21-49 ms) for Dct(-/-) mice and 22 ms (95% CI 11-32 ms) for Dct(+/-) mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95% CI 3.9-14.0 ms) in Dct(-/-) mice and by 1.5 ms (95% CI 0.7-2.3 ms) in Dct(+/-) mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct(-/-) mice. AA inducibility (89% vs 11%; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct(-/-) mice than in Dct(+/-) mice at baseline, but not different (22% vs 11%; P = 1.00) after apamin administration. Five of 8 (63%) induced atrial fibrillation episodes in Dct(-/-) mice had focal drivers. CONCLUSION: Apamin-sensitive SK current upregulation in Dct(-/-) mice plays an important role in the mechanism of AA.