Submitted on May 20, 2005
Accepted on July 20, 2005
Differential isoform expression of small conductance Ca2+-activated K+ channels, SK1, SK2 and SK3 channels in mouse atrial and ventricular myocytes
Dipika Tuteja1, Danyan Xu1, Valeriy Timofeyev1, Ling Lu1, Dipika Sharma1, Zhao Zhang2, Yanfang Xu3, Liping Nie4, Ana E Vazquez4, J. Nilas Young5, Kathryn A Glatter1, and Nipavan Chiamvimonvat6*
1 Internal Medicine, University of California, Davis, Davis, CA, USA
2 Internal Medicine, University of California, Davis, Davis, CA, USA; Physiology, University of Zhengzhou, China
3 Internal Medicine, University of California, Davis, Davis, CA, USA; Pharmacology, Hebei Medical University, China
4 Otolaryngology, University of California, Davis, Davis, CA, USA
5 Cardiothoracic Surgery, University of California, Davis, Davis, CA, USA
6 Internal Medicine, University of California, Davis, Davis, CA, USA; VANCHCS, Mather, CA, USA
* To whom correspondence should be addressed. E-mail: nchiamvimonvat{at}ucdavis.edu.
Small conductance Ca2+-activated K+ channels (SK channels, KCachannels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ (Ca2+i) with membrane potential. We have recently reported for the first time the functional existence of SK2(KCa2.2)channels in human and mouse cardiac myocytes. Here, we further report cloning of SK1(KCa2.1)and SK3(KCa2.3) channels from mouse atria and ventricles using reverse transcription polymerase chain reaction (RT-PCR). Full-length transcripts and their variants were detected for both SK1 and SK3 channels. Variants of mouse SK1 channel (mSK1) differ mainly in the C-terminal structure, affecting a portion of the sixth transmembrane segment (S6) and the calmodulin binding domain (CaMBD). Mouse SK3 channel (mSK3) differs not only in the number of polyglutamine repeats in the N-terminus, but also in the intervening sequences between the polyglutamine repeats. Full-length cardiac mSK1 and mSK3 show 99% and 91% nucleotide identity with those of mouse colon SK1 and SK3, respectively. Quantification of SK1, 2 and 3 transcripts between atria versus ventricles was performed using real-time quantitative RT-PCR from single isolated cardiomyocytes. SK1 transcript was found to be more abundant in the atria compared to the ventricles similar to the previously reported finding for SK2 channel. In contrast, SK3 showed similar level of expression in atria and ventricles. Taken together, our data are the first to report the presence of the three different isoforms of SK channels in the heart and the differential expression of SK1 and SK2 in mouse atria and ventricles. Due to the marked differential expression of SK channel isoforms in the heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.
