Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

Abstract

Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

• Authors: Philippe Magown, Basavaraj Shettar, Ying Zhang, Victor F Rafuse
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 8506 (Oct 13 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26460719 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Channelrhodopsins

Topics

• Animals
• Channelrhodopsins
• Female
• Mice, Inbred C57BL
• Mice, Transgenic
• Muscle Contraction
• Muscle Fibers, Skeletal (metabolism, radiation effects)
• Muscular Atrophy (therapy)
• Phototherapy
• Random Allocation