Characterization of a Voltage-Gated K+Channel β Subunit Expressed in Human Heart

Voltage-gated K+channels are important modulators of the cardiac action potential. However, the correlation of endogenous myocyte currents with K+channels cloned from human heart is complicated by the possibility that heterotetrameric α-subunit combinations and function-altering β subunits exist in native tissue. Therefore, a variety of subunit interactions may generate cardiac K+channel diversity. We report here the cloning of a voltage-gated K+channel β subunit, hKvβ3, from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat Kvβ1and Kvβ2subunits, respectively. Together these three Kvβ subunits share >82% identity in the carboxyl-terminal 329 aa and show low identity in the aminoterminal 79 aa. RNA analysis indicated that hKvβ3message is 2-fold more abundant in human ventricle than in atrium and is expressed in both healthy and diseased human hearts. Coinjection of hKvβ3with a human cardiac delayed rectifier, hKv1.5, in Xenopus oocytes increased inactivation, induced an 18-mV hyperpolarizing shift in the activation curve, and slowed deactivation (τ = 8.0 msec vs. 35.4 msec at -50 mV). hKvβ3was localized to human chromosome 3 by using a human/rodent cell hybrid mapping panel. These data confirm the presence of functionally important K+channel β subunits in human heart and indicate that β-subunit composition must be accounted for when comparing cloned channels with endogenous cardiac currents.