title: Some mechanisms of neuromuscular transmission
Creators: name: Cunnane, Thomas Christopher
Publisher: name: University of Glasgow
Year: 1979
Subjects: subject: Biological sciences, health and environmental sciences, nerve stimulation.

description: This thesis is divided into three main areas of research: (A) an electrical study of neuromuscular transmission in the vas deferens of the guinea-pig; (B) an examination of the electrical responses of the rabbit recotocccygeus to extrinsic parasympathetic nerve stimulation; (C) the effects of d-tubocurarine on skeletal neuromuscular transmission. (A) Excitatory junction potentials were recorded intracellularly in the guinea-pig vas deferens following stimulation of the hypogastric nerves. The effects of a number of drugs which block the effects of adrenergic nerve stimulation in other tissues were investigated. It is shown that the excitatory junction potential in the guinea-pig vas deferens is unlikely to be generated by noradrenaline acting on α or β-adrenoceptors. (B) The responses of the rabbit rectococcygeus muscle to stimulation of the extrinsic pelvic nerves have been investigated using intracellular micro-electrode recording techniques. Submaximal pelvic nerve stimulation evoked a depolarisation (excitatory junction potential) which was graded with stimulus strength and abolished by atropine (10-6 g/ml) and tetrodotoxin. Single supramaximal stimuli evoked action potentials associated with muscle contraction. In the presence of atropine, to abolish the excitatory junction potentials, supramaximal stimulation of the pelvic nerves evoked hyperpolarisations (inhibitory junction potentials) which were graded with stimulus strength and abolished by tetrodotoxin. The transmitter responsible for the inhibitory junction potentials is unknown. Phentolamine (10-5 g/ml) and propranolol (3 X 10-5 g/ml) in concentrations which block respectively α and β adrenoceptors and the adrenergic neurone blocking agent guanethidine (10-6 g/ml) were ineffective in blocking the inhibitory response. It is concluded that stimulation of the pelvic nerves to the rectococcygeus releases two transmitters, acetylcholine, responsible for the excitatory junction potential (and muscle contraction) and a non-adrenergic non- cholinergic transmitter which is the basis for the mechanical relaxation. (C) The final section of this thesis comprises a study of the effects of d-tubocurarine on skeletal neuromuscular transmission. The question asked was whether d-tubocurarine exerts a prejunctional effect on evoked transmitter release in addition to the classic view of post-junctional receptor blockade. Subthreshold end-plate potentials were recorded intracellularly from intact rat hemi-diaphragm preparations exposed to d-tubocurarine. The transmission process in intact hemi- diaphragms was compared with that in cut muscle preparations when neuromuscular transmission was studied in the absence of blocking agents. End-plate potential amplitude was well maintained in cut muscle preparations at all frequencies of stimulation (1 Hz - 50 Hz) in contrast to intact hemi-diaphragms exposed to d-tubocurarine. Two possible explanations of the results were discussed. First, that d-tubocurarine exerts a prejunctional effect on transmitter release and second that the 'apparent' decline in end-plate potential amplitude has a post-junctional origin, due to a shift to the right of the acetylcholine dose response curve. Similar experiments were performed on neuromuscular junctions of the frog sartorius and differences in the transmission process were observed. One explanation discussed is that there is a species difference in the pharmacological response to d-tubocurarine of frog and rat skeletal muscle. It is concluded that d-tubocurarine does not exert a prejunctional effect on transmitter release in the frog.