Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels

Coeli M.B. Lopes, Juan I. Remon, Alessandra Matavel, Jin Liang Sui, Inna Keselman, Emiliano Medei, Yuming Shen, Avia Rosenhouse-Dantsker, Tibor Rohacs, Diomedes E. Logothetis

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Neurotransmitter and hormone regulation of cellular function can result from a concomitant stimulation of different signaling pathways. Signaling cascades are strongly regulated during disease and are often targeted by commonly used drugs. Crosstalk of different signaling pathways can have profound effects on the regulation of cell excitability. Members of all the three main structural families of potassium channels: inward-rectifiers, voltage-gated and 2-P domain, have been shown to be regulated by direct phosphorylation and Gq-coupled receptor activation. Here we test members of each of the three families, Kir3.1/Kir3.4, KCNQ1/KCNE1 and TREK-1 channels, all of which have been shown to be regulated directly by phosphatidylinositol bisphosphate (PIP2). The three channels are inhibited by activation of Gq-coupled receptors and are differentially regulated by protein kinase A (PKA). We show that Gq-coupled receptor regulation can be physiologically modulated directly through specific channel phosphorylation sites. Our results suggest that PKA phosphorylation of these channels affects Gq-coupled receptor inhibition through modulation of the channel sensitivity to PIP2.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalChannels
Volume1
Issue number2
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Keywords

  • Forskolin
  • G proteinsensitive inwardly rectifying K channels (Kir3)
  • H89
  • KCNQ1/KCNE1 channels
  • Phosphatidyl inositol-bis-phosphate (PIP2)
  • Phosphorylation sites
  • PLC-dependent inhibition
  • Protein Kinase A (PKA)
  • TREK1 channels

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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  • Cite this

    Lopes, C. M. B., Remon, J. I., Matavel, A., Sui, J. L., Keselman, I., Medei, E., Shen, Y., Rosenhouse-Dantsker, A., Rohacs, T., & Logothetis, D. E. (2007). Protein kinase a modulates plc-dependent regulation and PIP2-sensitivity of K+ channels. Channels, 1(2), 124-134. https://doi.org/10.4161/chan.4322