OPEN-CHANNEL BLOCK OF HUMAN HEART HKV1.5 BY THE BETA-SUBUNIT HKV-BETA-1.2

Voltage-gated K+ currents in human heart are likely to derive from mul tisubunit complexes of pore-forming alpha-subunits with one or more au xiliary beta-subunits. We recently cloned a novel beta-subunit from hu man atrium, hKv beta 1.2 (K. Majumder, M. De Biasi, Z. Wang, and B. A. Wible. FEBS Lett. 361: 13-16, 1995), and showed that it interacts wit h channels in the Kv1 family. Here we characterize the interaction of hKv beta 1.2 with hKv1.5 in terms of a two-closed-state and one-open-s tate open channel block model. After coexpression in Xenopus oocytes, hKv1.5 currents were reduced in the presence of hKv beta 1.2, and at p ositive potentials an inactivation process was introduced. Deactivatio n kinetics of hKv1.5 were slowed, and there was an increased steepness with a -14-mV hyperpolarizing shift in the midpoint of steady-state a ctivation. The model was able to predict all the above features of the interaction of hKv1.5 and hKv beta l.2 as a result of rapid open chan nel block of activated channels. Understanding the mechanism of hKv be ta 1.2 action on heart K+ channels will further aid the development of the functional and pharmacological characterization of native cardiac K+ currents.