Molecular identification and functional analysis of a novel SK3 channel in rat heart

Abstract

Small-conductance Ca²⁺-activated K⁺ (SK; SK1, SK2 and SK3) channels are widely distributed throughout the body. However, its role in the heart is unclear. The aim of this study was to identify and analyze SK channels expressed in rat heart. Rat heart cDNA library was screened, and nine positive phage colonies were detected. Eight of nine cDNAs were identical to reported SK3. One cDNA was similar to SK3 but its N-terminal 19 amino acid was different. We termed it SK3-b. RT-PCR experiment showed that SK3-b was found in rat heart (3/33), but not in brain, liver, lung or intestine. SK3 and SK3-b were stably expressed in HEK293. Electrophysiological experiments reveled that voltage dependency and apamin sensitivity were not different between SK3 and SK3-b. However SK3-b was less sensitive to intracellular Ca²⁺ compared to SK3. Activation of PKA, PKG or PKC did not modify SK3 or SK3-b current. In immunohistochemistry by anti-SK3 antibody, which detect both SK3 and SK3-b, strong staining has been observed in the outermost layer of blood vessel and in adjacent cardiomyocytes of heart. Summary, we cloned SK3 and novel channel SK3-b from rat heart. These channels may contribute to cardiac function and metabolism. [Jpn J Physiol 55 Suppl:S130 (2005)]