Differential expression of small-conductance Ca²⁺-activated K⁺channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes

Abstract

Small-conductance Ca2+-activated K+ channels (SK channels, KCa channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ with membrane potential. We recently reported for the first time the functional existence of SK2 (KCa2.2) channels in human and mouse cardiac myocytes. Here, we report cloning of SK1 (KCa2.1) and SK3 (KCa2.3) channels from mouse atria and ventricles using 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 COOH-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 NH2 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, SK2, and SK3 transcripts between atria and ventricles was performed using real-time quantitative RT-PCR from single, isolated cardiomyocytes. SK1 transcript was found to be more abundant in atria compared with ventricles, similar to the previously reported finding for SK2 channel. In contrast, SK3 showed similar levels of expression in atria and ventricles. Together, our data are the first to indicate the presence of the three different isoforms of SK channels in heart and the differential expression of SK1 and SK2 in mouse atria and ventricles. Because of the marked differential expression of SK channel isoforms in heart, specific ligands for Ca2+-activated K+ currents may offer a unique therapeutic opportunity to modify atrial cells without interfering with ventricular myocytes.

Mechanisms underlying the cardiac pacemaker: the role of SK4 calcium-activated potassium channels

“…They mediate the afterhyperpolarization, which ends the action potential [142] . In the periphery, the SK channels are expressed in T-lymphocytes and atrial cells and play an important role in atrial repolarization [143][144][145][146][147][148] . SK1 channels are resistant to apamin [136] , and their unitary conductance varies from 11 to 26 pS depending on the experimental conditions [149][150][151] .…”

Regulation of Gene Transcription by Voltage-gated L-type Calcium Channel, Cav1.3

“…Specifically, several isoforms of small conductance Ca 2ϩ -activated K ϩ channels (SK or K Ca 2 channels) have been identified that underlie the Ca 2ϩ -activated K ϩ current (I K,Ca ) in human and mouse atrial myocytes (8,9). The SK channels are highly unique in that they are gated solely by changes in intracellular Ca 2ϩ ([Ca 2ϩ ] i ).…”

α-Actinin2 cytoskeletal protein is required for the functional membrane localization of a Ca2+-activated K+channel (SK2 channel)

“…SK channels represent a highly unique family of K ϩ channels, in that they are directly gated by changes in intracellular Ca 2ϩ concentration and hence function to integrate changes in Ca 2ϩ concentration with changes in K ϩ conductance and membrane potentials. SK channels have been shown to mediate afterhyperpolarizations in neurons (9,12,13) and action potential repolarization in cardiac tissues (14,15). Previous studies have provided strong support that ion channels are components of macromolecular complexes containing the main pore-forming and auxiliary subunits interacting with scaffolding and regulatory proteins that are linked to the cytoskeleton (16).…”