A NOVEL K-SUBUNIT (HKV-BETA-1.3) IS PRODUCED VIA ALTERNATIVE MESSENGER-RNA SPLICINGS( CHANNEL BETA)

Voltage-gated K+ channels can form multimeric complexes with accessory beta-subunits. We report here a novel K+ channel beta-subunit cloned from human heart, hKv beta 1.3, that has 74-83% overall identity with previously cloned beta-subunits. Comparison of hKv beta 1.3 with the p reviously cloned hKv beta 3 and rKv beta 1 proteins indicates that the carboxyl terminal 328 amino acids are identical, while unique variabl e length amino termini exist. Analysis of human beta-subunit cDNA and genomic nucleotide sequences confirm that these three beta-subunits ar e alternatively spliced from a common beta-subunit gene. Co-expression of hKv beta 1.3 in Xenopus oocytes with the delayed rectifier hKv1.5 indicated that hKv beta 1.3 has unique functional effects. This novel beta-subunit induced a time dependent inactivation during membrane vol tage steps to positive potentials, induced a 13-mV hyperpolarizing shi ft in the activation curve, and slowed deactivation (tau = 13 +/- 0.5 ms versus 35 +/- 1.7 ms at -40 mV). Most notably, hKv beta 1.3 convert ed the Kv1.5 outwardly rectifying current voltage relationship to one showing strong inward rectification. These data suggest that Kv channe l current diversity may arise from association with alternatively spli ced Kv beta-subunits. A simplified nomenclature for the K+ channel bet a-subunit subfamilies is suggested.