The Study of the Mechanism of Gamma-Aminobutyric Acid Inhibitory Effect on the Myotube Formation Process in Cell Culture

Gamma-aminobutyric acid (GABA) is commonly regarded as a signaling molecule in CNS synapses, where it plays the role of the main inhibitory neurotransmitter in the mature brain and is involved in the process of neurogenesis. Recently, data have been obtained indicating that GABA can also be involved in the early stages of the skeletal muscle development process. In the present study performed on rat cultured myocytes, we analyzed the effect of exogenous GABA on the process of myocyte fusion into myotubes as assessed by the morphometric parameter fusion index. Addition of GABA to the cell culture resulted in a significant concentration-dependent inhibition, up to complete cessation, of myotube formation. Of possible proteins that can mediate this effect, GABAA receptors and GABA transporters (GAT-2) have been considered. Evidence of the presence of these proteins on cultured cells was obtained by immunohistochemistry methods. The blockade of GABAA receptors by gabazine had no effect on the fusion index, and GABA exerted its inhibitory effect in the presence of gabazine. Inhibition of GABA transporters by nipecotic acid, in itself, reduced the myocyte fusion index; however, there was no effect of GABA in the presence of this blocker of GABA transporters. The data obtained are consistent with the hypothesis about the participation of GABA in the early stages of skeletal muscle development. Results suggest that the inhibitory effect of exogenous GABA may be due to an increase in its concentration in the sarcoplasm, since both the addition of a GABA transporter inhibitor and an increase in the extracellular concentration of GABA inhibited the formation of myotubes.

Automated summary

The study indicates that GABA may play a role in the early stages of skeletal muscle development by inhibiting the fusion of myocytes into myotubes.