The molecular basis of the potassium ion (K+) channels that generate r
epolarization in heart tissue remains uncertain, in part because of th
e molecular diversity of the voltage-gated K+ channel family. In our i
nvestigation, we used fluorescent labeled oligonucleotide probes to pe
rform in situ hybridization studies on enzymatically isolated myocytes
to determine the identify, regional distribution, and cellular distri
bution of voltage-gated K+ channel, alpha-subunit, mRNA expressed in f
erret heart. The regions studied were from the sinoatrial node (SA), r
ight and left atrium, right and left ventricle, and interatrial and in
terventricular septa. Kv1.5 and Kv1.4 were the most widely distributed
K+ channel transcripts in the ferret heart (present in approximately
70%-86% and approximately 46%-95% of tested myocytes, respectively), f
ollowed by Kv1.2, Kv2.1, and Kv4.2. In addition, many myocytes contain
transcripts for Kv1.3, Kv2.2, Kv4.1, Kv5.1, and members of the Kv3 fa
mily. Kv1.1, Kv1.6, and Kv6.1 were rarely expressed in working myocyte
s, but were more commonly expressed in SA nodal cells. Two other trans
cripts whose genes have been implicated in the long QT syndrome, erg a
nd KvLQT1, were common in all regions (approximately 41%-58% and 52%-7
2%, respectively). These results show that both the diversity and hete
rogeneity of K+ channel mRNA in heart tissue is greater than previousl
y suspected.