CHARACTERIZATION OF A VOLTAGE-GATED K-SUBUNIT EXPRESSED IN HUMAN HEART( CHANNEL BETA)

Voltage-gated K+ channels are important modulators of the cardiac acti on potential. However, the correlation of endogenous myocyte currents with K+ channels cloned from human heart is complicated by the possibi lity that heterotetrameric cr-subunit combinations and function-alteri ng beta subunits exist in native tissue, Therefore, a variety of subun it interactions may generate cardiac K+ channel diversity, We report h ere the cloning of a voltage-gated K+ channel beta subunit, hK(v) beta (3), from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat K-v beta(1) and K-v beta(2) subunits, respectively, Together these three K-v beta subunits share >82% identity in the carboxyl-terminal 329 aa and show low iden tity in the amino-terminal 79 aa, RNA analysis indicated that hK(v) be ta(3) message is 2-fold more abundant in human ventricle than in atriu m and is expressed in both healthy and diseased human hearts, Coinject ion of hK(v) beta(3) with a human cardiac delayed rectifier, hK(v)1.5, in Xenopus oocytes increased inactivation, induced an 18-mV hyperpola rizing shift in the activation curve, and slowed deactivation (tau = 8 .0 msec vs. 35.4 msec at -50 mV). hK(v) beta(3) was localized to human chromosome 3 by using a human/rodent cell hybrid mapping panel, These data confirm the presence of functionally important K+ channel beta s ubunits in human heart and indicate that beta-subunit composition must be accounted for when comparing cloned channels with endogenous cardi ac currents.