Protein kinase A phosphorylation alters Kvbeta1.3 subunit-mediated inactivation of the Kv1.5 potassium channel.

Kwak YG, Hu N, Wei J, George AL, Grobaski TD, Tamkun MM, Murray KT
J Biol Chem. 1999 274 (20): 13928-32

PMID: 10318802 · DOI:10.1074/jbc.274.20.13928

The human Kv1.5 potassium channel forms the IKur current in atrial myocytes and is functionally altered by coexpression with Kvbeta subunits. To explore the role of protein kinase A (PKA) phosphorylation in beta-subunit function, we examined the effect of PKA stimulation on Kv1.5 current following coexpression with either Kvbeta1.2 or Kvbeta1.3, both of which coassemble with Kv1.5 and induce fast inactivation. In Xenopus oocytes expressing Kv1.5 and Kvbeta1.3, activation of PKA reduced macroscopic inactivation with an increase in K+ current. Similar results were obtained using HEK 293 cells which lack endogenous K+ channel subunits. These effects did not occur when Kv1.5 was coexpressed with either Kvbeta1.2 or Kvbeta1.3 lacking the amino terminus, suggesting involvement of this region of Kvbeta1.3. Removal of a consensus PKA phosphorylation site on the Kvbeta1.3 NH2 terminus (serine 24), but not alternative sites in either Kvbeta1.3 or Kv1.5, resulted in loss of the functional effects of kinase activation. The effects of phosphorylation appeared to be electrostatic, as replacement of serine 24 with a negatively charged amino acid reduced beta-mediated inactivation, while substitution with a positively charged residue enhanced it. These results indicate that Kvbeta1.3-induced inactivation is reduced by PKA activation, and that phosphorylation of serine 24 in the subunit NH2 terminus is responsible.

MeSH Terms (17)

Amino Acid Substitution Animals Cell Line Consensus Sequence Cyclic AMP-Dependent Protein Kinases Enzyme Activation Humans Kv1.3 Potassium Channel Kv1.5 Potassium Channel Mutagenesis, Site-Directed Oocytes Phosphorylation Potassium Channels Potassium Channels, Voltage-Gated Serine Structure-Activity Relationship Xenopus laevis

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