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

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 previously cloned hKv beta 3 and rKv beta 1 proteins indicates that the carboxyl terminal 328 amino acids are identical, while unique variable length amino termini exist. Analysis of human beta-subunit cDNA and genomic nucleotide sequences confirm that these three beta-subunits are 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 voltage steps to positive potentials, induced a 13-mV hyperpolarizing shift 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 converted the Kv1.5 outwardly rectifying current voltage relationship to one showing strong inward rectification. These data suggest that Kv channel current diversity may arise from association with alternatively spliced Kv beta-subunits. A simplified nomenclature for the K+ channel beta-subunit subfamilies is suggested.