On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: involvement of GTP-binding proteins.
The molecular mechanisms underlying activation of a K+ channel by adenosine (Ado) and acetylcholine (ACh) were examined in single atrial cells of guinea-pig. Whole cell clamp and patch clamp techniques were used to characterize the K+ channel. In the whole cell clamp conditions, Ado and ACh increased the K+ channel current in a dose-dependent manner. The maximum responses and the apparent dissociation constants were different for Ado and ACh activations of the current. Theophylline blocked activation of the K+ current by Ado, while atropine blocked ACh-activation, indicating that two different membrane receptors were involved. Measurements of the conductance and kinetic properties of both whole cell and single channel currents indicate that Ado and ACh regulate the same K+ channels. In "inside-out" patch conditions, GTP was required in the intracellular side of the membrane for activation of the K+ channel by agonists (present in the patch electrode). The A promoter of pertussis toxin inhibited the channel activation only when NAD was also present. Furthermore, GTP-gamma S, a non-hydrolyzable GTP analogue, gradually caused activation of the K+ channel in the absence of agonists. Therefore, it was concluded that Ado and m-ACh receptors link with the same population of K+ channels via GTP-binding proteins Ni and/or No in the atrial cell membrane.
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006168:Guinea Pigs; D006325:Heart Atria; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009116:Muscarine / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D011188:Potassium / Q000378:metabolism*
D007473:Ion Channels; D009116:Muscarine; D019204:GTP-Binding Proteins; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium