Evaluation of intrinsic modulation of synaptic transmission by ATP in mouse fast twitch muscle.

This study aims to evaluate whether endogenous ATP or adenosine modulates the neurotransmission and contractile function of mouse phrenic nerve-diaphragm. Bath application of ATP (1 mM) and alpha, beta-methylene ATP (m-ATP, 0.1 mM) elevated muscle tones, depressed contractions (approximately 12%), and depolarized muscle membranes (approximately 20 mV). Adenosine (1 mM) or low concentrations of ATP (0.1 mM) had no effect. In a low Ca2+ media, ATP caused prolonged inhibitions of endplate potentials (EPPs), whereas m-ATP augmented EPPs while both agents produced slight effects in normal Tyrode solution. When applied by puff ejection, ATP and m-ATP additionally elicited fast transient suppressions of EPPs in association with inhibitions of high K+-evoked releases of miniature EPPs. Blockades of P2 purinoceptors with suramin antagonized all the effects of ATP and m-ATP except the prolonged inhibitions of EPPs induced by ATP, which were antagonized instead by 8-cyclopentyl-1,3-dipropylxanthine (CPDPX), an A1 adenosine receptor antagonist. Suramin and CPDPX did not change contractions nor alter EPPs evoked by a low- or high-frequency nerve stimulation. The results indicate that exogenously applied ATP and m-ATP, via activations of distinct pre- and postsynaptic purinoceptors, exert inhibitory and facilitatory pharmacological modulations on the mature neuromuscular junction. However, because of intrinsic high efficiency of the synaptic transmission under physiological conditions, endogenously released ATP and its degradation product-adenosine-do not build up to concentrations high enough to alter motor functions.