Skeletal muscle contractions, which permit breathing, feeding, speaking or moving, require action potentials triggered by the muscle voltage-gated sodium channels (Na_V) in mammals. Lacking these muscle channels is lethal at birth in human and mouse. The small Danio rerio fish, commonly referred to as zebrafish, is a well-recognized model for studying human disorders and testing the effect of small chemical compounds on swim. Indeed, it is considered that fast skeletal muscles of zebrafish function as mammal muscles. Dr Sophie Nicole in the team “Ion channels, neuronal excitability and channelopathies” led by Philippe Lory, in collaboration with Prof Bruno Allard in the team “Excitability and calcium signaling in normal and diseased skeletal muscle” led by Vincent Jacquemond at the Neuromyogen Institute (Lyon) demonstrated that this statement is wrong.

The authors compared Na_V channels and action potentials properties of fast skeletal muscle fibers of adult zebrafish to mouse muscle fibers. They found that Na_V channels and action potentials were less efficient in zebrafish muscle fibers compared to mouse fibers at physiological membrane potentials. Calcium transients in zebrafish fibers did not have the “all or none” aspect observed in mouse fibers, and were still observed when Na_V channels were inhibited. Finally, the absence of Na_V channels in zebrafish muscles did not induce mortality or swim changes in fish, whereas the lack of muscle Na_V channels in mouse is lethal at birth.

The data show that zebrafish fast muscle fibers are tonic with efficient fast muscles contraction in the absence of muscle Na_V channels and action potentials. Zebrafish muscle fibers are innervated by several motoneurons with several synapses (called neuromuscular junctions) along all the fiber: synaptic transmission would be sufficient to induce muscle contraction. In contrast, mammalian muscle fibers are phasic and are innervated by a single motoneuron. They require action potentials, generated by Na_V channels at the centrally-located synapse, which propagate along the myofiber to induce efficient contraction.

With more than 600 skeletal muscles, the muscle mass represents around 40% of the human body. The usefulness of muscle Na_V channels for efficient locomotion of zebrafish has then to be taken into consideration when studying the biological effect of a small chemical compounds in order to avoid adverse muscular effects when pursuing the studies in mammals.

This work has just been published in the journal PLoS Biology.

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