Guanylyl cyclase stimulatory coupling to K_Cachannels

Abstract

We coexpressed the human large-conductance, calcium-activated K (K(Ca)) channel (alpha- and beta-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 alpha-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.

Kv Channels Contribute to Nitric Oxide- and Atrial Natriuretic Peptide-Induced Relaxation of a Rat Conduit Artery

“…In addition, Alioua et al (1998) have demonstrated that activation of MaxiK channels by PKG in vivo involves a direct phosphorylation of the channel protein. Consistent with this idea, Nara et al (2000) showed that mutations of serine residues of the MaxiK pore-forming ␣-subunit suppressed NO-or ANP-induced enhancement of the channel activity.…”

The Appearance of a Protein Kinase A-regulated Splice Isoform of slo Is Associated with the Maturation of Neurons That Control Reproductive Behavior

“…They differ only in the presence or absence of a unique consensus phosphorylation site for PKA, located in the large carboxyl tail domain that plays a role in Ca 2ϩ sensing and acts as a partner for protein-protein interactions (31)(32)(33)(34). Previous work has shown that Slo channels in other species are modulated by a number of different protein kinases (35)(36)(37)(38)(39)(40)(41)(42) and the nature of this modulation can differ between tissues. For example, PKA activates BK channels in smooth muscle as well as in neurons but inhibits channel activity in endocrine cells of the anterior pituitary (43)(44)(45)(46).…”

Identification and localization of BK-β subunits in the distal nephron of the mouse kidney

“…Additionally, FIKS is significantly attenuated in mice null for the BK-␤1 subunit (BK-␤1 Ϫ/Ϫ ) (39,40). It is not understood how BK-␤1 increases channel activity in response to high flow; however, BK-␤1 bestows increased Ca 2ϩ sensitivity to BK (34) and confers sensitivity of BK to activation by protein kinase G (PKG) (20,33).…”