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Nat Commun ; 10(1): 115, 2019 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-30631052

RESUMEN

The Ca2+-activated Cl- channel (CaCC) TMEM16A/Anoctamin 1 (ANO1) is expressed in gastrointestinal epithelia and smooth muscle cells where it mediates secretion and intestinal motility. However, ANO1 Cl- conductance has never been reported to play a role in skeletal muscle. Here we show that ANO1 is robustly expressed in the highly evolved skeletal musculature of the euteleost species zebrafish. We characterised ANO1 as bonafide CaCC which is activated close to maximum by Ca2+ ions released from the SR during excitation-contraction (EC) coupling. Consequently, our study addressed the question about the physiological advantage of implementation of ANO1 into the euteleost skeletal-muscle EC coupling machinery. Our results reveal that Cl- influx through ANO1 plays an essential role in restricting the width of skeletal-muscle action potentials (APs) by accelerating the repolarisation phase. Resulting slimmer APs enable higher AP-frequencies and apparently tighter controlled, faster and stronger muscle contractions, crucial for high speed movements.


Asunto(s)
Potenciales de Acción/fisiología , Anoctamina-1/metabolismo , Calcio/metabolismo , Músculo Esquelético/fisiología , Proteínas de Pez Cebra/metabolismo , Animales , Anoctamina-1/genética , Cloruros/metabolismo , Humanos , Modelos Biológicos , Contracción Muscular/fisiología , Músculo Esquelético/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferencia de ARN , Retículo Sarcoplasmático/metabolismo , Proteínas de Pez Cebra/genética
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