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Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels

Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels,10.1093/bja/aef163,British Journal of Anaesthesia,A. Scholz

Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels   (Citations: 50)
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Local anaesthetics have been used clinically for well over a century, but the molecular mechanisms by which they alter specific functions of the peripheral nerve system remained unclear for a long time. Investigations during the last few decades presented evidence implicating the sodium (Na+) channel protein as a target for specific, clinically important, local anaesthetic effects on mammalian neurones. In this review I will present the state of knowledge of the action of local anaesthetics at the molecular level, with an emphasis on Na+ channels. After a brief survey of the history of concepts of local anaesthetic actions, the structure of the Na+ channel will be described with regard to its function in order to understand the recent findings that have followed the description of the amino acid sequence of the Na+ channel protein.46 At clinically relevant concentrations local anaesthetics can also affect potassium (K+) and calcium (Ca2+) channels, which might help explain some of their side-effects. General anaesthetics also interact with these targets (ion channels), but differences in selectivity compared with local anaesthetics have been reported. Current findings indicate that local anaesthetics also act on intracellular mechanisms, which raises the question of whether these might explain toxicity and other side-effects.
Journal: British Journal of Anaesthesia - BRIT J ANAESTH , vol. 89, no. 1, pp. 52-61, 2002
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