Academic Journal

Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the repolarization process of atrial myocytes

التفاصيل البيبلوغرافية
العنوان: Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the repolarization process of atrial myocytes
المؤلفون: Zhang, Xiao-Dong, Timofeyev, Valeriy, Li, Ning, Myers, Richard E., Zhang, Dai-Min, Singapuri, Anil, Lau, Victor C., Bond, Chris T., Adelman, John, Lieu, Deborah K., Chiamvimonvat, Nipavan
بيانات النشر: Oxford University Press
سنة النشر: 2014
المجموعة: HighWire Press (Stanford University)
مصطلحات موضوعية: Ion channels and arrhythmias
الوصف: Aims Small conductance Ca2+-activated K+ channels (K Ca 2 or SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ ( ) with membrane potentials. We have recently reported the functional expression of SK channels in human and mouse cardiac myocytes. Additionally, we have found that the channel is highly expressed in atria compared with the ventricular myocytes. We demonstrated that human cardiac myocytes expressed all three members of SK channels (SK1, 2, and 3); moreover, the different members are capable of forming heteromultimers. Here, we directly tested the contribution of SK3 to the overall repolarization of atrial action potentials. Methods and results We took advantage of a mouse model with site-specific insertion of a tetracycline-based genetic switch in the 5′ untranslated region of the KCNN3 (SK3 channel) gene ( SK3T/T ). The gene-targeted animals overexpress the SK3 channel without interfering with the normal profile of SK3 expression. Whole-cell, patch-clamp techniques show a significant shortening of the action potential duration mainly at 90% repolarization (APD 90 ) in atrial myocytes from the homozygous SK3T/T animals. Conversely, treatment with dietary doxycycline results in a significant prolongation of APD 90 in atrial myocytes from SK3T/T animals. We further demonstrate that the shortening of APDs in SK3 overexpression mice predisposes the animals to inducible atrial arrhythmias. Conclusion SK3 channel contributes importantly towards atrial action potential repolarization. Our data suggest the important role of the SK3 isoform in atrial myocytes.
نوع الوثيقة: text
وصف الملف: text/html
اللغة: English
Relation: http://cardiovascres.oxfordjournals.org/cgi/content/short/101/2/317; http://dx.doi.org/10.1093/cvr/cvt262
DOI: 10.1093/cvr/cvt262
الاتاحة: http://cardiovascres.oxfordjournals.org/cgi/content/short/101/2/317
https://doi.org/10.1093/cvr/cvt262
Rights: Copyright (C) 2014, European Society of Cardiology
رقم الانضمام: edsbas.9FC79105
قاعدة البيانات: BASE