Potassium (K+) channels are critical for a variety of cell functions, including modulation of action potentials, determination of resting membrane potential, and development of memory and learning. In addition to their role in regulating myocyte excitability, cardiac K+ channels control heart rate and coronary vascular tone and are implicated in the development of arrhythmias. We report here the cloning and sequencing of a k+ channel gene, KCNA1, derived from a human cardiac cDNA library and the chromosomal localization of the corresponding genomic clone. Oligonucleotides based on a delayed rectifier K+ channel gene were used in PCR reactions with human genomic DNA to amplify the S4-S6 regions of several different K+ channel genes. These sequences were used to isolate clones from a human cardiac cDNA library. We sequenced one of these clones, HCK1. HCK1 contains putative S2-S6 domains and shares approximately 70% sequence homology with previously isolated Shaker homologues. HCK1 was used to screen human cosmid libraries and a genomic clone was isolated. By sequencing the genomic clones, a putative S1 domain and translation initiation sequences were identified. Genomic mapping using human-rodent somatic cell panels and in situ hybridization with human metaphase chromosomes have localized KCNA1 to the distal short arm of human chromosome 12. This work is an important step in the study of human cardiac K+ channel structure and function and will be of use in the study of human inherited disease.

The Shaker related alpha-subunit subfamily of human voltage-activated KCNA-channels is encoded by several genes in the human genome. We have isolated yeast artificial chromosomes (YACs) spanning approximately 1 Mb of human chromosome 12p13 DNA. Molecular biological characterization of the YAC-insert DNAs revealed that three KCNA genes--KCNA1, KCNA5, KCNA6--are clustered within approximately 300 kb of insert-DNA derived from chromosome 12p13. The KCNA gene cluster has been conserved between mouse and human. The three KCNA genes in the cluster are transcribed from the same DNA strand being arranged in a head-to-tail fashion in the order KCNA6-KCNA1-KCNA5. Northern blot analyses of the KCNA1, KCNA5 and KCNA6 mRNAs in different human brain areas show that the genes are distinctly expressed. Therefore, they may be transcribed independently of each other.

>gnl|TC-DB|Q09470 1.A.1.2.12 Potassium voltage-gated channel subfamily A member 1
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