Activation of Muscarinic Potassium Currents by ATP$\gamma $S in Atrial Cells

• Published in: Science (American Association for the Advancement of Science) Vol. 242; no. 4877; pp. 443 - 445
• Main Authors: Otero, Angela S., Breitwieser, Gerda E., Szabo, Gabor
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 21.10.1988; American Association for the Advancement of Science
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Adenylyl Imidodiphosphate - pharmacology; Agonists; Analysis; Animals; Atrial Function; Biochemistry; Biological and medical sciences; Cell regulation; Cellular control mechanisms; Cholinergic receptors; Dialysis; Electric potential; Enzymes; Fundamental and applied biological sciences. Psychology; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Triphosphate - analogs & derivatives; Guanosine Triphosphate - metabolism; Guanosine Triphosphate - pharmacology; Heart; Heart - physiology; Heart Atria - drug effects; Heart cells; In Vitro Techniques; Ion channels; Membrane Potentials - drug effects; Nucleotides; Perfusion; Phosphates; Phosphorylation; Potassium; Potassium Channels - drug effects; Potassium Channels - physiology; Rana catesbeiana; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - physiology; Thionucleotides - metabolism; Thionucleotides - pharmacology; Vertebrates: cardiovascular system; Voltage-clamp technique (Electrophysiology); Heart; Transmembrane current; Vertebrata; Amphibia; Toad; Salientia; Muscarinic receptor; Circulatory system; ATP; Potassium; Heart cell
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3051383

Intracellular perfusion of atrial myocytes with adenosine 5$^{\prime}$-($\gamma $-thio) triphosphate (ATP$\gamma $S), an ATP analog, elicits a progressive increase of the muscarinic potassium channel current, I$_{\text{K(M)}}$, in the absence of agonists. In this respect, ATP$\gamma $S mimics the actions of guanosine triphosphate (GTP) analogs, which produce direct, persistent activation of the guanyl nucleotide--binding (G) protein controlling the K$_{(\text{M})}^{+}$ channel. The effect of ATP$\gamma $S on I$_{\text{K(M)}}$, however, differs from that produced by GTP analogs in two aspects: it requires relatively large ATP$\gamma $S concentrations, and it appears after a considerable delay, suggesting a rate-limiting step not present in similar experiments performed with guanosine 5$^{\prime}$-($\gamma $-thio) triphosphate (GTP$\gamma $S). Incubation of atrial homogenates with [$^{35}$S]ATP$\gamma $S leads to formation of significant amounts of [$^{35}$S]GTP$\gamma $S, suggesting that activation of I$_{\text{K(M)}}$ by ATP$\gamma $S arises indirectly through its conversion into GTP$\gamma $S by cellular enzymes. ATP$\gamma $S is often used to demonstrate the involvement of protein phosphorylation in the control of various cellular processes. The finding that cytosolic application of ATP$\gamma $S can also lead to G-protein activation implies that experiments with ATP$\gamma $S must be interpreted with caution.