Variability and failure of neurotransmission in the diaphragm of mdx mice.
Loss of specific muscle force and evidence of myopathy are present in the diaphragm of mdx mice by 4 weeks of age. The neuromuscular junction of dystrophic muscle also shows structural abnormalities at this age. Whether these structural alterations result in neural transmission abnormalities is currently unclear, particularly at physiological firing frequencies. Thus, we investigated the extent of neurotransmission variability and failure during 35 and 100 Hz stimulation in the diaphragm of 6 to 8-month-old mdx mice in comparison to age-matched controls. Neurotransmission failure was similar across groups at both stimulation frequencies, despite the presence of disrupted post-synaptic acetylcholine receptors (AChRs). Neural transmission variability, however, measured by comparing variation in force production during direct muscle stimulation compared to variation in force production during phrenic nerve stimulation was significantly greater in dystrophic muscle. Together, these results suggest that neurotransmission is maintained at physiologic firing frequencies in dystrophic muscle, but the precision of neurotransmission is attenuated. A reduced density of functional AChRs likely underlies the increase in neurotransmission variability.
Department of Rehabilitation Science, School of Public Health and Health Professions, University at Buffalo, Kimball Tower Rm. 515, 3435 Main St., Buffalo, NY 14214-3079, USA. kep7@buffalo.edu
Kirkwood E
KE
Personius
Robert P
RP
Sawyer
D000818:Animals; D002038:Bungarotoxins / Q000493:pharmacokinetics; D003964:Diaphragm / Q000503:physiopathology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000502:physiology / Q000528:radiation effects; D010791:Phrenic Nerve / Q000503:physiopathology / Q000528:radiation effects; D011950:Receptors, Cholinergic / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D002038:Bungarotoxins; D011950:Receptors, Cholinergic