Tetanic failure due to decreased endogenous adenosine A2A tonus operating neuronal Cav1 (L‐type) influx in Myasthenia gravis

摘要: J. Neurochem. (2011) 117, 797–811. Abstract In healthy motor endplates, tetanic depression is overcome by tonic adenosine A2A-receptor-mediated facilitation of transmitter release. The A2A receptor operates a coordinated shift from fast-desensitizing Cav2.1 (P/Q) calcium influx to long-lasting CaV1 (L) channels on nerve terminals. This study aimed at investigating whether receptors-operated Ca2+ via (L)-type contribute sustain acetylcholine release evoked 50 Hz-bursts in toxin-induced Myasthenia gravis (TIMG) rats. In contrast control animals, inhibition [3H]acetylcholine (ACh) the CaV2.1 channel blocker, ω-Agatoxin IVA (100 nM), TIMG rats had higher magnitude than that observed with nifedipine (1 μM). Adenosine deaminase (0.5 U/mL) and antagonist, ZM 241385 (50 nM), decreased [3H]ACh similar amount rats, but their effects were smaller myasthenic animals. precursor, AMP (100 μM), increased (∼40%) ACh both Blockade A2A, not A1, receptors prevented AMP-induced release; (1 μM) mimicked effect antagonist. Video-microscopy studies designed measure real-time exocytosis using FM4-64 fluorescent dye fully supported radiochemical data. Thus, impairment adaptive may failure parallels reduction tonus which might be restored exogenous application AMP.