Two voltage-gated K+ channel cDNAs, HK1 and HK2, were isolated from human ventricular libraries, encoding proteins of 653 and 605 amino acids with distinct regional expression patterns.
The cloning of human ventricular voltage-gated K+ channels HK1 and HK2 provides a molecular basis for understanding cardiac repolarization and potential targets for antiarrhythmic drugs.
K+ channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. In the heart these channels are responsible for the rapid repolarizing phases of the action potential and are the targets of several antiarrhythmic drugs. Full-length cDNA clones were isolated from human ventricular libraries that encode two voltage-gated K+ channels. These two cDNAs, designated HK1 and HK2, encode proteins of 653 and 605 amino acids, respectively. HK1 is the human equivalent (98% identity) of an inactivating K+ channel previously described in rat heart (RHK1) whereas the HK2 channel is 86% identical to a cloned rat brain K+ channel (Kv1). The only amino acid sequence identity (72%) between HK1 and HK2 is within the central region containing the membrane spanning domains. Northern blot analysis of human mRNA indicated that HK1 is slightly more abundant in ventricle than atrium whereas HK2 is much more abundant in atrium relative to ventricle. Both channel transcripts are present in ventricle at levels equivalent to voltage-gated Na+ channels. Analysis of the gene encoding HK1 suggests the coding sequence is intronless and is represented once in the human genome.
Tamkun et al. (1991) studied this question. Molecular cloning of HK1 and HK2 cDNAs was evaluated on Characterization of HK1 and HK2 cDNAs. Two voltage-gated K+ channel cDNAs, HK1 and HK2, were isolated from human ventricular libraries, encoding proteins of 653 and 605 amino acids with distinct regional expression patterns.