Résumé :
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Communication n° 338. Evidence indicates that extracellular ATP may have relevant functions in skeletal muscle, even though the physiological role and distribution of specific signalling pathway elements is not well known. Normally, ATP is released from cells through mechanisms that include exocytosis, transporters and stretch-activated channels. The action of ATP is under control of ectonucleotidases, a class of extracellular enzymes, present in almost all cells, devoted to the degradation of nucleotides. Extracellular ATP exerts its action by activating specific receptors, named P2X and P2Y. Activation of distinct P2 receptors is associated to a variety of biological responses, including neurotransmission in the central and peripheral nervous system, nociception, smooth muscle contraction, immune responses, and platelets aggregation. In vitro experiments showed that substantial ATP is released and rapidly hydrolyzed after electrical stimulation of rat muscle fibres. The nucleotide thus appears to exert important autocrine/paracrine actions after each muscle fibre contraction. RT-PCR and Western blot analyses demonstrate that P2X4 receptor, an extracellular ATP-regulated cell membrane channel permeable to Ca2+, is expressed in skeletal muscle, at a level that was higher in slow- than in fast-twitch muscles. Immunofluorescence demonstrated that P2X4 has an intracellular localization and confocal analysis revealed that the receptor co-localizes with the T-tubule membrane DHP receptor. The presence in such structure of an ATP-operated cation channels suggested that P2X4 could participate in modulating muscle contraction. Present results show that application of ATP-degrading enzymes (hexokinase/apyrase), inhibitors of P2X receptors or Ca2+-free conditions abolished the progressive twitch tension potentiation produced in soleus muscle by low-frequency (0.05 Hz) stimulation. These data reveal that ATP-mediated Ca2+ entry, most likely through P2X4 receptor, sustains contractility of skeletal muscle during prolonged exercise.
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