Intracellular ATP modulates desensitization of acetylcholine receptors controlling chloride current in Lymnaea neurons.
Chloride current activated by nicotinic acetylcholine receptors (AChR) was examined in dialysed voltage-clamp neurons of Lymnaea stagnalis. Fast superfusion of acetylcholine (ACh) evoked an inward current rapidly rising to a peak followed by a decline due to desensitization. When adenosine triphosphate with Mg2+ (MgATP, 2-10 mM) was added intracellularly the peak of the ACh-induced current was increased and its decay was slowed down. ATP without Mg2+ did not affect desensitization. Mg2+ alone accelerated desensitization. Intracellular treatment with an inhibitor of ATP synthesis, sodium arsenate, increased the desensitization rate and decreased the peak current. MgATP after arsenate wash-out restored the initial characteristics of the response; a mixture of glycolytic substrates had a similar effect. A non-hydrolysable analogue of ATP, adenosine [gamma-thio]triphosphate mimicked ATP action after arsenate removal but was weaker; another non-hydrolysable analogue, adenylyl imidodiphosphate, did not affect desensitization at all. Intracellular treatment of the neurons with alkaline phosphatase accelerated current decay. The data suggest that a change in intracellular ATP concentration modulates AChR desensitization via an enzymatic process that might be phosphorylation of AChR or some associated protein(s). Involvement of Ca2+ homeostasis cannot be excluded. The results are compared with the data obtained on vertebrate tissues under conditions promoting phosphorylation.
Lozovaya
N A
NA
Laboratory of Nerve Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow region.
Vulfius
C A
CA
Ilyin
V I
VI
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001149:Arsenates / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004594:Electrophysiology; D007700:Kinetics; D008195:Lymnaea; D008274:Magnesium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*
D001149:Arsenates; D002712:Chlorides; D011950:Receptors, Cholinergic; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase; D008274:Magnesium; C025657:arsenic acid