By functional coexpression screening of a rat cDNA library in Xenopus oocytes, we have cloned a protein (KCRF: K Channel Regulatory Factor) that reduces currents of several K(+) channels: G protein-activated GIRK1/4 (K(ir)3.1/K(ir)3.4), inward rectifier IRK1 (K(ir)2.1), and voltage-dependent K(V)1.1/K(V)beta1.1. KCRF did not modulate two other K(+) channels: ROMK1 (K(ir)1.1) and GIRK1/2 (K(ir)3.1/K(ir)3.2) and the voltage-dependent L-type Ca(2+) channels. Western blot analysis showed that KCRF is ubiquitous in rat tissues. Biochemical and electrophysiological experiments revealed that coexpression of KCRF causes a decrease in the level of expression of IRK1 and K(V)1.1/K(V)beta1.1 proteins in the oocytes.
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