ras p21 and GAP inhibit coupling of muscarinic receptors to atrial K+ channels.
The signal-transducing G protein Gk couples muscarinic receptors to K+ (K+[ACh]) channels in atrial cells. Recombinant human ras p21 GAP (GTPase activating protein) at subnanomolar concentrations inhibited GTP-dependent channel opening in isolated atrial cell membranes. This inhibition depended on interaction of GAP with ras p21 in the isolated membranes. In addition, recombinant ras p21 proteins blocked the currents; this effect could be blocked by prior incubation of membranes with specific anti-GAP antibodies. We therefore propose that ras p21 GTP complexed with GAP (ras p21-GAP) blocks K+[ACh] currents. The channel block could be overcome by GTP gamma S activation of endogenous Gk; this indicates that ras p21-GAP does not interfere with interaction of Gk with the K+[ACh] channel directly, but prevents coupling of the muscarinic receptor to endogenous Gk.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030.
A
A
Yatani
K
K
Okabe
P
P
Polakis
R
R
Halenbeck
F
F
McCormick
A M
AM
Brown
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D020690:GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D015689:Oncogene Protein p21(ras) / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D015221:Potassium Channels; D011506:Proteins; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D020703:ras GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D015689:Oncogene Protein p21(ras)