title: Anaesthetic tricaine acts preferentially on neural voltage-gated sodium channels and fails to block directly evoked muscle contraction.
abstract: Movements in animals arise through concerted action of neurons and skeletal muscle. General anaesthetics prevent movement and cause loss of consciousness by blocking neural function. Anaesthetics of the amino amide-class are thought to act by blockade of voltage-gated sodium channels. In fish, the commonly used anaesthetic tricaine methanesulphonate, also known as 3-aminobenzoic acid ethyl ester, metacaine or MS-222, causes loss of consciousness. However, its role in blocking action potentials in distinct excitable cells is unclear, raising the possibility that tricaine could act as a neuromuscular blocking agent directly causing paralysis. Here we use evoked electrical stimulation to show that tricaine efficiently blocks neural action potentials, but does not prevent directly evoked muscle contraction. Nifedipine-sensitive L-type Cav channels affecting movement are also primarily neural, suggesting that muscle Nav channels are relatively insensitive to tricaine. These findings show that tricaine used at standard concentrations in zebrafish larvae does not paralyse muscle, thereby diminishing concern that a direct action on muscle could mask a lack of general anaesthesia.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Seetharamaiah
authors.initials: S
authors.lastname: Attili
authors.affiliation: Randall Division of Cell and Molecular Biophysics, Guy's Campus, King's College London, London, United Kingdom.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Hughes
mesh_terms: D062365:Aminobenzoates / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D062365:Aminobenzoates; D000777:Anesthetics; D061566:Voltage-Gated Sodium Channels; C003636:tricaine
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