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Research ArticleCARDIOVASCULAR

Modulation of the Human Kv1.5 Channel by Protein Kinase C Activation: Role of the Kvβ1.2 Subunit

Christine P. Williams, NingNing Hu, Wangzhen Shen, Amy B. Mashburn and Katherine T. Murray
Journal of Pharmacology and Experimental Therapeutics August 2002, 302 (2) 545-550; DOI: https://doi.org/10.1124/jpet.102.033357
Christine P. Williams
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NingNing Hu
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Wangzhen Shen
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Amy B. Mashburn
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Katherine T. Murray
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Abstract

Kv1.5 is the principal molecular component of IKur, an atrial-specific K+ current in human myocytes that is suppressed by activation of protein kinase C (PKC). We examined the effect of phorbol 12-myristate 13-acetate (PMA), a direct activator of PKC, on Kv1.5 current. Although PMA had minimal effect when Kv1.5 was expressed alone, K+ currents derived from coexpression of Kvβ1.2 (but not another closely related β subunit, Kvβ1.3) with Kv1.5 were markedly reduced by PMA, associated with a small depolarizing shift in the voltage dependence of channel activation. Additional experiments with an inactive stereoisomer, 4α-PMA, and the PKC inhibitor chelerythrine indicated that the effects of PMA were mediated by PKC activation. Assembly of Kv1.5 in vivo with both β subunits was demonstrated, and all three K+ channel proteins were substrates for phosphorylation by PKC. These results demonstrate that coexpression of Kvβ1.2 enhances the response of Kv1.5 to PKC activation and that direct phosphorylation of K+ channel subunits is a potential molecular basis for the effect. Furthermore, they suggest that Kvβ1.2 may be a component of the IKur complex in human atrium.

Footnotes

  • This work was supported by grants from the National Institutes of Health (R01 HL47599) and the American Heart Association (Southeast Affiliate).

  • DOI: 10.1124/jpet.102.033357

  • Abbreviations:
    AF
    atrial fibrillation
    PKC
    protein kinase C
    PMA
    phorbol 12-myristate 13-acetate
    PKA
    cAMP-dependent protein kinase (protein kinase A)
    HA
    hemagglutinin
    • Received January 18, 2002.
    • Accepted April 25, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 302 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 2
1 Aug 2002
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Research ArticleCARDIOVASCULAR

Modulation of the Human Kv1.5 Channel by Protein Kinase C Activation: Role of the Kvβ1.2 Subunit

Christine P. Williams, NingNing Hu, Wangzhen Shen, Amy B. Mashburn and Katherine T. Murray
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 545-550; DOI: https://doi.org/10.1124/jpet.102.033357

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Research ArticleCARDIOVASCULAR

Modulation of the Human Kv1.5 Channel by Protein Kinase C Activation: Role of the Kvβ1.2 Subunit

Christine P. Williams, NingNing Hu, Wangzhen Shen, Amy B. Mashburn and Katherine T. Murray
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 545-550; DOI: https://doi.org/10.1124/jpet.102.033357
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