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Effects of membrane cholesterol-targeting chemicals on skeletal muscle contractions evoked by direct and indirect stimulation. | LitMetric

Effects of membrane cholesterol-targeting chemicals on skeletal muscle contractions evoked by direct and indirect stimulation.

J Muscle Res Cell Motil

Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, 2/31 Lobachevsky St, Kazan, 420111, Russia.

Published: December 2024

AI Article Synopsis

  • Cholesterol is essential for the plasma membrane and helps form lipid rafts, which play a crucial role in muscle contraction and nerve communication in skeletal muscle.
  • In experiments involving mouse diaphragm, lower concentrations of cholesterol-depleting agents did not significantly impact muscle contractions, but higher concentration (10 mM) notably weakened the contraction response during nerve stimulation.
  • The study suggests that severe cholesterol depletion primarily disrupts neuromuscular communication rather than affecting the contractility of muscle fibers themselves.

Article Abstract

Cholesterol is one of the major components of plasma membrane, where its distribution is nonhomogeneous and it participates in lipid raft formation. In skeletal muscle cholesterol and lipid rafts seem to be important for excitation-contraction coupling and for neuromuscular transmission, involving cholesterol-rich synaptic vesicles. In the present study, nerve and muscle stimulation-evoked contractions were recorded to assess the role of cholesterol in contractile function of mouse diaphragm. Exposure to cholesterol oxidase (0.2 U/ml) and cholesterol-depleting agent methyl-β-cyclodextrin (1 mM) did not affect markedly contractile responses to both direct and indirect stimulation at low and high frequency. However, methyl-β-cyclodextrin at high concentration (10 mM) strongly decreased the force of both single and tetanus contractions induced by phrenic nerve stimulation. This decline in contractile function was more profoundly expressed when methyl-β-cyclodextrin application was combined with phrenic nerve activation. At the same time, 10 mM methyl-β-cyclodextrin had no effect on contractions upon direct muscle stimulation at low and high frequency. Thus, strong cholesterol depletion suppresses contractile function mainly due to disturbance of the neuromuscular communication, whereas muscle fiber contractility remains resistant to decline.

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Source
http://dx.doi.org/10.1007/s10974-024-09675-7DOI Listing

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