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Sandona D, Danieli-Betto D, Germinario E, Biral D, Martinello
T, Lioy A, Tarricone E, Gastaldello S, Betto R. The T-tubule
membrane ATP-operated P2X4 receptor influences contractility of skeletal
muscle. FASEB J. 2005;Jul;19(9):1184-1186.
Department of Biomedical and Experimental Sciences, University
of Padova, Padova, Italy.
Evidence indicates that extracellular ATP may have relevant functions
in skeletal muscle, even though the physiological role and distribution
of specific signaling pathway elements are not well known. The present
work shows that P2X4 receptor, an extracellular ATP-regulated cell membrane
channel permeable to Ca2+, is expressed in several tissues of the rat,
including skeletal muscle. A specific antibody detected a protein band
of approximately 60 kDa. Immunofluorescence demonstrated that P2X4 has
an intracellular localization, and confocal analysis revealed that the
receptor colocalizes with the T-tubule membrane DHP receptor. Considering
that the natural agonist of P2X4 is ATP, we explored if changes of extracellular
ATP levels could occur in contracting skeletal muscle to regulate the
channel. In vitro experiments showed that substantial ATP is released
and rapidly hydrolyzed after electrical stimulation of rat muscle fibers.
Results show that the presence of ATP-degrading enzymes (hexokinase/apyrase),
inhibitors of P2X receptors or Ca2+-free conditions, all 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, may play an important
role in modulating the contractility of skeletal muscle.
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Abstracts