Denervation effects on choline depolarization of muscle membrane

Portela, A.; Perez, Rogelio; Nallar, R; González, J. C.; Stewart, Peter A.; Vicente, Josefina; Lonchampt, P

doi:10.1007/bf01899087

Cited by 4 publications

(2 citation statements)

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“…Fischer et al showed that the α7 nAChR subtype is playing an important role in the rat muscle development for the endplate formation and/or stabilization [33]. It has been reported that choline causes depolarization of muscle membranes [35], [36], and that the choline-evoked depolarization is enhanced after the muscle denervation [33], [37]. Choline also increases the intracellular Ca 2+ concentration at the muscle endplates [38].…”

Section: Discussionmentioning

confidence: 99%

acr-23 Encodes a Monepantel-Sensitive Channel in Caenorhabditis elegans

et al. 2013

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Monepantel is a member of the recently identified class of anthelmintics known as the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro-intestinal nematodes in sheep including those that are resistant to the classical anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23 and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of monepantel. With this discovery it became possible to investigate the mode of action of monepantel in nematodes at the molecular level. In the present study, we show that a C. elegans mutant acr-23 strain is fully rescued by expressing the wild-type acr-23 gene. Moreover, we present a new mutant allele, and characterize acr-23 alleles genetically. We also show that acr-23 is expressed in body wall muscle cells, and provide therefore a possible explanation for the paralysis caused by monepantel. Furthermore, genetic evidence suggests that the chaperone RIC-3 is required for expression of full monepantel resistance. Finally, we present reconstitution of the C. elegans ACR-23 receptor in Xenopus laevis oocytes and provide direct evidence of its modulation by monepantel. Conversely, co-injection of the chaperone RIC-3 had no impact for channel reconstitution in X. laevis oocytes. These results reinforce the involvement of the ACR-23 family in the mode of action of monepantel and advance our understanding of this new class of anthelmintics.

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Section: Discussionmentioning

confidence: 99%

acr-23 Encodes a Monepantel-Sensitive Channel in Caenorhabditis elegans

et al. 2013

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“…In fact, choline acts as a weak agonist for muscle‐type, α3β4, and α4β4 nAChRs expressed in Xenopus oocytes (Papke et al 1996; Alkondon et al 1997; Zwart & Vijverberg, 2000). It has been reported that choline causes depolarization of muscle membranes (Del Castillo & Katz, 1957; Portela et al 1970), and that the choline‐evoked depolarization is enhanced after the muscle denervation (Portela et al 1969; Fischer et al 1999). Choline also increases the intracellular Ca 2+ concentration at the muscle endplates (Dezaki et al 1999).…”

Section: Discussionmentioning

confidence: 99%