Abstract
Small-conductance Ca$^2+$-activated K$^+$ channels (SK channels,
KCa channels) have been reported in excitable cells, where they aid
in integrating changes in intracellular Ca$^2+$ 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 Ca$^2+$-activated K$^+$
currents may offer a unique therapeutic opportunity to modify atrial
cells without interfering with ventricular myocytes.
- ,
- 16055520
- acid
- amino
- animals,
- atria,
- calcium-activated,
- cardiac,
- cells,
- channels,
- comparative
- cultured,
- data,
- expression
- extramural,
- gene
- gov't,
- heart
- male,
- mice,
- molecular
- myocytes,
- n.i.h.,
- non-u.s.
- potassium
- regulation,
- research
- sequence
- sequence,
- study,
- support,
- ventricles,
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