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• W1605222204 abstract "ATP is released from skeletal muscle during exercise, a discovery dating back to 1969. Surprisingly, few studies have examined the effects of extracellular ATP on mature mammalian skeletal muscle. This electrophysiological study examined the effects of extracellular ATP on fully innervated rat levator auris longus using two intracellular microelectrodes. The effects of ATP were determined by measuring the relative changes of miniature endplate potentials (mEPPs) and voltage responses to step current pulses in individual muscle fibres. Exposure to ATP (20 μ m ) prolonged the mEPP falling phase by 31 ± 7.5% (values ± s.d. , n = 3 fibres). Concurrently, the input resistance increased by 31 ± 2.0% and the time course of the voltage responses increased by 59 ± 3.0%. Analogous effects were observed using 2 and 5 μ m ATP, and on regions distal from the neuromuscular junction, indicating that physiologically relevant levels of ATP enhanced electrical signalling over the entire muscle fibre. The effects of extracellular ATP were blocked by 200 μ m anthracene‐9‐carboxylic acid, a chloride channel inhibitor, and reduced concentrations of extracellular chloride, indicating that ATP inhibited chloride channels. A high affinity agonist for P2Y receptors, 2‐methylthioadenosine‐5′‐ O ‐diphosphate (2MeSADP), induced similar effects to ATP with an EC 50 of 160 ± 30 n m . The effects of 250 n m 2MeSADP were blocked by 500 n m MRS2179, a specific P2Y 1 receptor inhibitor, suggesting that ATP acts on P2Y 1 receptors to inhibit chloride channels. The inhibition of chloride channels by extracellular ATP has implications for muscle excitability and fatigue, and the pathophysiology of myotonias." @default.
• W1605222204 created "2016-06-24" @default.
• W1605222204 creator A5044478293 @default.
• W1605222204 date "2009-11-30" @default.
• W1605222204 modified "2023-10-17" @default.
• W1605222204 title "Extracellular ATP inhibits chloride channels in mature mammalian skeletal muscle by activating P2Y₁receptors" @default.
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• W1605222204 doi "https://doi.org/10.1113/jphysiol.2009.179275" @default.
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