Comparison of binding and block produced by alternatively spliced Kvbeta1 subunits.
Voltage-gated K+ (Kv) channels consist of alpha subunits complexed with cytoplasmic Kvbeta subunits. Kvbeta1 subunits enhance the inactivation of currents expressed by the Kv1 alpha subunit subfamily. Binding has been demonstrated between the C terminus of Kvbeta1.1 and a conserved segment of the N terminus of Kv1.4, Kv1.5, and Shaker alpha subunits. Here we have examined the interaction and functional properties of two alternatively spliced human Kvbeta subunits, 1.2 and 1.3, with Kvalpha subunits 1.1, 1.2, 1.4, and 1.5. In the yeast two-hybrid assay, we found that both Kvbeta subunits interact specifically through their conserved C-terminal domains with the N termini of each Kvalpha subunit. In functional experiments, we found differences in modulation of Kv1alpha subunit currents that we attribute to the unique N-terminal domains of the two Kvbeta subunits. Both Kvbeta subunits act as open channel blockers at physiological membrane potentials, but hKvbeta1.2 is a more potent blocker than hKvbeta1.3 of Kv1.1, Kv1.2, Kv1.4, and Kv1. 5. Moreover, hKvbeta1.2 is sensitive to redox conditions, whereas hKvbeta1.3 is not. We suggest that different Kvbeta subunits extend the range over which distinct Kv1alpha subunits are modulated and may provide a variable mechanism for adjusting K+ currents in response to alterations in cellular conditions.
Wang
Z
Z
Rammelkamp Center for Research, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio 44109-1998, USA. bwible@research.mhmc.org
Kiehn
J
J
Yang
Q
Q
Brown
A M
AM
Wible
B A
BA
D017398:Alternative Splicing; D001483:Base Sequence; D001923:Brain Chemistry; D006801:Humans; D051664:Kv1.3 Potassium Channel; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D012260:Ribonucleases / Q000378:metabolism
C097044:KCNAB1 protein, human; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012260:Ribonucleases