Enhancement of mouse diaphragm contractility in the presence of antagonists of GABAA and GABAB receptors.

Abstract

What is the central question of this study? Do GABA receptors play any role at the neuromuscular junction? What is the main finding and its importance? In the presence of either ionotropic or metabotropic GABA receptor antagonists, diaphragm muscle force production elicited by stimulating the motor nerve at ≥50Hz was increased. Our data indicate the presence of GABAergic signalling at the neuromuscular junction. Despite the signalling role of GABA in the brain and spinal cord, the role of this molecule in the peripheral nervous system and, in particular, at the neuromuscular junction remains practically unexplored. In the present work, the force of mouse diaphragm contractions was measured in the presence of blockers of metabotropic GABAB receptors (CGP55845) and ionotropic GABAA receptors (picrotoxin) with various patterns of indirect and direct stimulation of muscle by trains of 40 pulses delivered at 10, 20, 50 and 70Hz. It was found that neither blocker affected the diaphragm contractility caused by indirect stimulation through the motor nerve at 10 and 20Hz. However, when the stimulation frequency was increased to 50 or 70Hz, the force of subsequent contractions in the train (when compared with the amplitude of contraction in response to the first pulse) was increased by both CGP55845 and picrotoxin. With direct stimulation of the diaphragm, no significant changes in the contraction force were detected at any frequency used. The results obtained support the following conclusions: (i) pharmacological inhibition of GABA receptors increases the contractile activity of skeletal muscle; and (ii) frequency-dependent enhancement of GABA receptor activation takes place in the region of the neuromuscular junction.