The discovery of hKvβ1.3 and its functional effects on hKv1.5 demonstrates that alternative splicing of Kv β-subunits contributes to K+ channel current diversity in the human heart.
Voltage-gated K+ channels can form multimeric complexes with accessory β-subunits. We report here a novel K+ channel β-subunit cloned from human heart, hKvβ1.3, that has 74-83% overall identity with previously cloned β-subunits. Comparison of hKvβ1.3 with the previously cloned hKvβ3 and rKvβ1 proteins indicates that the carboxyl-terminal 328 amino acids are identical, while unique variable length amino termini exist. Analysis of human β-subunit cDNA and genomic nucleotide sequences confirm that these three β-subunits are alternatively spliced from a common β-subunit gene. Co-expression of hKvβ1.3 in Xenopus oocytes with the delayed rectifier hKv1.5 indicated that hKvβ1.3 has unique functional effects. This novel β-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 (τ = 13 ± 0.5 ms versus 35 ± 1.7 ms at -40 mV). Most notably, hKvβ1.3 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 β-subunits. A simplified nomenclature for the K+ channel β-subunit subfamilies is suggested. Voltage-gated K+ channels can form multimeric complexes with accessory β-subunits. We report here a novel K+ channel β-subunit cloned from human heart, hKvβ1.3, that has 74-83% overall identity with previously cloned β-subunits. Comparison of hKvβ1.3 with the previously cloned hKvβ3 and rKvβ1 proteins indicates that the carboxyl-terminal 328 amino acids are identical, while unique variable length amino termini exist. Analysis of human β-subunit cDNA and genomic nucleotide sequences confirm that these three β-subunits are alternatively spliced from a common β-subunit gene. Co-expression of hKvβ1.3 in Xenopus oocytes with the delayed rectifier hKv1.5 indicated that hKvβ1.3 has unique functional effects. This novel β-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 (τ = 13 ± 0.5 ms versus 35 ± 1.7 ms at -40 mV). Most notably, hKvβ1.3 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 β-subunits. A simplified nomenclature for the K+ channel β-subunit subfamilies is suggested.
England et al. (1995) studied this question.