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Am J Physiol Heart Circ Physiol 275: H1963-H1970, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 6, H1963-H1970, December 1998

Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing

Wei Kong1, Sunny Po1, Toshio Yamagishi1, M. Dominique Ashen1, Gail Stetten2, and Gordon F. Tomaselli1

1 Department of Medicine, Section of Molecular and Cellular Cardiology, and 2 Department of Gynecology and Obstetrics, Johns Hopkins University, Baltimore, Maryland 21205

The transient outward K+ current (Ito) in the heart is responsible for the initial phase of repolarization and for setting the plateau voltage of the ventricular action potential. Recently, Kv4.3 has emerged as the leading candidate alpha -subunit gene that underlies Ito in larger mammals such as dogs and humans. We have cloned the human Kv4.3 homolog and describe a carboxyl-terminal splice variant that inserts 19 amino acids with a consensus protein kinase C (PKC) phosphorylation site into the protein after the last membrane-spanning segment. The coding region of Kv4.3 is comprised of at least five exons and is located on chromosome 1p13.3. In the basal state the basic biophysical properties of both of the splice variants are identical.

potassium channel; Kv4.2; Kv4.3; Xenopus oocytes; heterologous expression; fluorescence in situ hybridization; chromosome 1


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