Potentiation by ATP of the postsynaptic acetylcholine response at developing neuromuscular synapses in Xenopus cell cultures.

Abstract

1. Extracellular application of ATP to developing Xenopus neuromuscular synapses in culture resulted in a marked increase in the amplitude and frequency of spontaneous synaptic currents, using whole-cell recording. 2. The postsynaptic action of ATP was examined by studying the response of isolated muscle cells to iontophoretically applied acetylcholine (ACh). ATP enhanced the responses of the muscle membrane to ACh. The order of potency for various nucleotides (ATP = ADP > AMP, adenosine, GTP) suggests that ATP acts through P2-purinoceptors. The effect of ATP on whole-cell currents was also abolished by the protein kinase inhibitor H-7. 3. Single-channel measurements indicate that ATP increased the mean open time of lowconductance ACh channels. No change in the conductance of ACh channels was observed. 4. Local application of ATP to one region of the elongated myocyte surface resulted in potentiated ACh responses only at the ATP-treated region, suggesting that the cytosolic second messengers were effectively confined within the muscle cytoplasm. 5. The results of the present study suggest that ATP released from the nerve terminals may potentiate the ACh response of developing muscle cells during the early phase of synaptogenesis, and that the action of ATP can be restricted to the subsynaptic region exposed to the secreted ATP.

Non‐additive interaction between nicotinic cholinergic and P2X purine receptors in guinea‐pig enteric neurons in culture

“…This observation suggests that ATP could directly modify nAChR activity by binding to the nAChR rather by binding to the P2X receptor. Indeed, it has been shown that ATP enhances responses mediated at nAChRs at the somatic neuronmuscular junction (Akasu et al 1981;Igusa, 1988;Lu & Smith, 1991;Fu, 1994) and in bullfrog sympathetic ganglia (Akasu & Koketsu, 1985). However, a positive allosteric effect of ATP on nAChR receptor function is inconsistent with the negative interaction between nAChRs and P2X receptors reported here.…”

The Signaling Pathways Mediated by P2Y Nucleotide Receptors in the Formation and Maintenance of the Skeletal Neuromuscular Junction

“…When ATP was focally applied to 1-day-old Xenopus nerve-muscle coculture, a marked increase in the amplitude and decay time of spontaneous synaptic currents was revealed, while on myocytes, it potentiated the response to the applied ACh [52]. The ATP-potentiated ACh current in Xenopus nerve-muscle coculture was believed to be mediated by an intracellular protein kinase C pathway, because the potentiation was reversed by treating the cultures with a protein kinase C inhibitor H7 [53]. The ATP-induced effects were blocked by antagonists of P2 receptors and by protein kinase C inhibitors, and were not blocked by adenosine (P1-type) receptor antagonists [52,54].…”

Modelling endplate currents: dependence on quantum secretion probability and decay of miniature current

“…These two factors were chosen and examined together because both of them are variable during natural patterns of synaptic activity (Van der Kloot 1988a; Giniatullin et al 1993) and both of them might be changed by a number of pharmacological agents (e.g. Fu 1994;Van der Kloot 1990). …”