A receptor that is highly specific for extracellular ATP in developing chick skeletal muscle in vitro

1. Extracellular adenosine 5'-triphosphate (ATP) activated an early excitatory conductance followed by a late potassium conductance in developing chick skeletal muscle. A series of ATP analogues were tested for their ability to activate these two conductances. All compounds tested were either agonists for both responses or for neither. Furthermore, the potency of agonists was similar for the two responses. 2. The order of potency for agonists was ATP approximately adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S) approximately 2-methylthio-ATP (2-CH3S-ATP) greater than 2'-deoxy-ATP approximately 3'-deoxy-ATP greater than adenosine 5'-tetraphosphate (ATP-OPO3) approximately adenosine 5'-diphosphate (ADP). Many other ATP analogues were not agonists. 3. Activation of the excitatory response did not require divalent cations. Furthermore, the concentration-response relation of the excitatory response was similar when ATP was applied as the free anion of ATP (ATP4-) or complexed with a divalent cation (M.ATP2-). 4. Three antagonists of the ATP response were characterized. 8-Br-ATP was a weak antagonist, while 2',3'-dialdehyde-ATP and DIDS (4,4'-diisocyanatostilbene-2,2'-disulphonic acid) were potent irreversible inhibitors. The two conductances were equally affected by these antagonists. 5. These results suggest that both ATP responses are activated through the same receptor type, or two very similar receptors.