Guanylyl cyclase stimulatory coupling to K(Ca) channels

M. Nara, P. D.K. Dhulipala, G. J. Ji, U. R. Kamasani, Y. X. Wang, S. Matalon, M. I. Kotlikoff

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44 Citations (Scopus)

Abstract

We coexpressed the human large-conductance, calcium-activated K (K(Ca)) channel (α- and β-subunits) and rat atrial natriuretic peptide (ANP) receptor genes in Xenopus oocytes to examine the mechanism of guanylyl cyclase stimulatory coupling to the channel. Exposure of oocytes to ANP stimulated whole cell K(Ca) currents by 21 ± 3% (at 60 mV), without altering current kinetics. Similarly, spermine NONOate, a nitric oxide donor, increased K(Ca) currents (20 ± 4% at 60 mV) in oocytes expressing the channel subunits alone. Stimulation of K(Ca) currents by ANP was inhibited in a concentration-dependent manner by a peptide inhibitor of cGMP-dependent protein kinase (PKG). Receptor/channel stimulatory coupling was not completely abolished by mutating the cAMP-dependent protein kinase phosphorylation site on the α-subunit (S869; Nars M, Dhulipals PD, Wang YX, and Kotlikoff MI. J Biol Chem 273: 14920-14924, 1998) or by mutating a neighboring consensus PKG site (S855), but mutation of both residues virtually abolished coupling. Spermine NONOate also failed to stimulate channels expressed from the double mutant cRNAs. These data indicate that nitric oxide donors stimulate K(Ca) channels through cGMP-dependent phosphorylation and that two serine residues (855 and 869) underlie this stimulatory coupling.

Original languageEnglish
Pages (from-to)C1938-C1945
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number6 48-6
DOIs
Publication statusPublished - 2000

Keywords

  • Calcium-activated potassium channels
  • Ion channel
  • Mutagenesis
  • Smooth muscle
  • cGMP-dependent protein kinase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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