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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Schlesinger, F. et al.

Schlesinger, Krampfl, Haeseler, Dengler, Bufler,

Competitive and open channel block of recombinant nAChR channels by different antibiotics.

Various antibiotics may impair neuromuscular transmission, provoking symptoms of myasthenia in patients with a compromised safety margin of the synaptic transmission, but little is known about the underlying mechanisms at the molecular level. Using a modified patch-clamp technique in combination with an ultrafast system for solution exchange we investigated the functional interaction of gentamicin, penicillin G, tetracycline, erythromycin and ceftriaxone with nAChR transiently transfected into HEK293 cells as a potential molecular target. Gentamicin, penicillin G, tetracycline and erythromycin induced a combination of open channel and competitive block of nAChR channel currents whereas ceftriaxone had no effect. The IC50 for the competitive block was close to or within the range of clinically relevant concentrations. Except for erythromycin the open channel block was observed only at higher concentrations. From our in-vitro results we conclude that competitive inhibition of nAChR channels by antibiotics is an important mechanism underlying the impairment of neuromuscular transmission under clinical conditions.[1]

References

Competitive and open channel block of recombinant nAChR channels by different antibiotics. Schlesinger, F., Krampfl, K., Haeseler, G., Dengler, R., Bufler, J. Neuromuscul. Disord. (2004) [Pubmed]

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