TitleLevamisole and ryanodine receptors. II: An electrophysiological study in Ascaris suum.
Publication TypeJournal Article
Year of Publication2010
AuthorsPuttachary, S, Robertson, AP, Clark, CL, Martin, RJ
JournalMol Biochem Parasitol
Volume171
Issue1
Pagination8-16
Date Published2010 May
ISSN1872-9428
KeywordsAnimals, Anthelmintics, Ascaris suum, Caffeine, Calcium, Chlorides, Cholinergic Agonists, Electrophysiological Phenomena, Furylfuramide, Levamisole, Mecamylamine, Models, Biological, Ryanodine, Ryanodine Receptor Calcium Release Channel
Abstract

Resistance to antinematodal drugs like levamisole has increased and there is a need to understand what factors affect the responses to these anthelmintics. In our previous study, we examined the role of ryanodine receptors in muscle contraction pathways. Here we have examined interactions of levamisole receptors, ryanodine receptors (RyRs), the excitatory neuropeptide AF2, and coupling to electrophysiological responses. We examined the effects of a brief application of levamisole on Ascaris suum body muscle under current-clamp. The levamisole responses were characterized as an initial primary depolarization, followed by a slow secondary depolarizing response. We examined the effects of AF2 (KHEYLRFamide), 1 microM applied for 2 min. We found that AF2 potentiated the secondary response to levamisole and had no significant effect on the primary depolarization. Further, the reversal potentials observed during the secondary response suggested that more than one ion was involved in producing this potential. AF2 potentiated the secondary response in the presence of 30 microM mecamylamine suggesting the effect was independent of levamisole sensitive acetylcholine receptors. The secondary response, potentiated by AF2, appeared to be dependent on cytoplasmic events triggered by the primary depolarization. Ion-substitution experiments showed that the AF2 potentiated secondary response was dependent on extracellular calcium and chloride suggesting a role for the calcium-activated anion channel. Caffeine mimicked the AF2 potentiated secondary response and 0.1 microM ryanodine inhibited it. 1.0 microM ryanodine increased spiking showing that it affected membrane excitability. A model is proposed showing ryanodine receptors mediating effects of AF2 on levamisole responses.

DOI10.1016/j.molbiopara.2009.12.006
Alternate JournalMol. Biochem. Parasitol.
PubMed ID20064567
PubMed Central IDPMC2839013
Grant ListR01 AI047194 / AI / NIAID NIH HHS / United States
R01 AI047194-10 / AI / NIAID NIH HHS / United States