ATP-dependent activation of atrial muscarinic K+ channels in the absence of agonist and G-nucleotides.
While opening of cardiac muscarinic K+ channels is mediated by a guanine nucleotide-binding protein, GK, and normally requires both ACh and cytosolic GTP, we demonstrate that in the absence of agonist and G-nucleotides guinea-pig atrial muscarinic K+ channels are activated by cytosolic ATP (K50 = 224 microM). This activation involves a phosphorylating reaction and is most probably related to a transphosphorylation by a nucleoside diphosphate kinase (NDPK) from ATP to GK-bound GDP. This ATP-induced response is completely inhibited by nanomolar concentrations of GDP or GTP, suggesting a G-nucleotide specific binding site on NDPK.
Heidbüchel
H
H
Laboratory of Physiology, KU Leuven, Belgium.
Callewaert
G
G
Vereecke
J
J
Carmeliet
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D015221:Potassium Channels / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
D015221:Potassium Channels; D011976:Receptors, Muscarinic; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D000109:Acetylcholine