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, hK(v)β₃, from adult human left ventricle that shows 84% and 74% amino acid sequence identity with the previously cloned rat K(v)β₁ and K(v)β₂ subunits, respectively. Together these three K(v)β subunits share >82% identity in the carboxyl-terminal 329 aa and show low identity in the aminoterminal 79 aa. RNA analysis indicated that hK(v)β₃ message is 2-fold more abundant in human ventricle than in atrium and is expressed in both healthy and diseased human hearts. Coinjection of hK(v)β₃ with a human cardiac delayed rectifier, hK(v)1.5, 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). hK(v)β₃ 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 β subunits in human heart and indicate that β-subunit composition must be accounted for when comparing cloned channels with endogenous cardiac currents.