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.
Highlights
In the 18th century, Luigi Galvani laid the foundations of biophysics by discovering that electrical stimuli can trigger muscular contraction, transmit to muscles via nerves and are generated by animals themselves [1]
We report the impact of tricaine on zebrafish skeletal muscle at early developmental stages
At the normal concentrations used for anaesthesia, tricaine does not prevent muscle contraction or interfere with excitation-contraction coupling
Summary
In the 18th century, Luigi Galvani laid the foundations of biophysics by discovering that electrical stimuli can trigger muscular contraction, transmit to muscles via nerves and are generated by animals themselves [1]. Voltage gated ion channels are key to the generation of action potentials (reviewed in [2]). An action potential propagates rapidly along the neural axon, stimulating the release of the neurotransmitter, which in turn elicits an action potential in the muscle fibre plasma membrane. This second action potential propagates via the transverse-tubule system deep into the fibre, where the dihyropyridine receptor (DHPR) acts as a voltage sensor that causes release of Ca++ from sarcoplasmic reticulum into the cytoplasm. Following Galvani, muscle contraction can be directly activated by external electric stimulation that triggers action, controlling immediate contraction events and longer term muscle gene expression [5,6,7,8]
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