Endogenous adenosine modulates stimulation-induced depression at the frog neuromuscular junction.
1. Endogenous adenosine, which is produced by enzymatic degradation of ATP released from synaptic vesicles, has been shown to be a potent inhibitor of acetylcholine release from motor nerve terminals. It has been proposed that this auto-inhibition mechanism might contribute significantly to tetanic stimulation-induced depression. 2. Levels of facilitation and depression during a 20 Hz stimulus train differ greatly in different terminals, but are strongly and non-linearly correlated with the terminal's release characteristics (the amount of transmitter released per unit terminal length, or 'release efficacy'). There is a weaker, approximately linear, correlation between depression and release efficacy at 2 Hz stimulation. 3. The effects of both endogenous and exogenously applied adenosine are also highly variable for different nerve terminals. We have shown that much of this variability can be attributed to the release efficacy of each terminal in the case of endogenous effects, and to the size of the nerve terminal in the case of exogenously applied adenosine receptor agonists. 4. When nerve terminals are pooled according to their individual release characteristics, endogenous adenosine can be shown to contribute significantly to stimulation-induced depression of release primarily in terminals that release enough transmitter to generate significant levels of adenosine, but do not release so much transmitter that depletion of releasable quanta is severe.
Jerry Lewis Neuromuscular Research Center, Department of Physiology, UCLA School of Medicine 90024.
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Grinnell
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D003864:Depression, Chemical; D004558:Electric Stimulation; D009411:Nerve Endings / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology*; D011894:Rana pipiens; D011983:Receptors, Purinergic / Q000502:physiology; D013569:Synapses / Q000502:physiology
D018377:Neurotransmitter Agents; D011983:Receptors, Purinergic; D000241:Adenosine