Faculty Collaboration Database

Phosphorylation-independent regulation of cardiac IK by guanine nucleotides and isoproterenol. Am J Physiol 1992 Apr;262(4 Pt 2):H1298-302

Date

04/01/1992

Pubmed ID

1314511

DOI

10.1152/ajpheart.1992.262.4.H1298

Scopus ID

2-s2.0-0026752064 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

We tested for direct G protein regulation of delayed rectifier K+ (IK) channels, by measuring IK currents in guinea pig ventricular cells using patch-clamp procedures. In excised inside-out patches, IK was enhanced by adding guanosine triphosphate or guanosine 5'-O-(3-thiotriphosphate) to the cytoplasmic side, even in the presence of phosphorylation inhibitors. Enhancement of patch IK did not require extracellular agonist; however, enhancement of IK was also seen when isoproterenol was included in the pipette solution. Whole cell IK currents were increased by isoproterenol when phosphorylation pathways were blocked. These data demonstrate that guanine nucleotides and beta-adrenergic agonists can enhance IK by a phosphorylation-independent pathway. Our findings are consistent with a direct coupling of the beta-adrenergic receptor to the cardiac IK channel via a membrane-delimited G protein pathway, in addition to the well-established indirect pathway.

Author List

Freeman LC, Kwok WM, Kass RS

Author

Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cyclic AMP
Electrophysiology
Guanine Nucleotides
Guanosine 5'-O-(3-Thiotriphosphate)
Guanosine Triphosphate
Isoproterenol
Myocardium
Phosphorylation
Potassium Channels
Thionucleotides