Effects of catecholamines on the neuromuscular junction in the rat diaphragm

Abstract

1. The effects of noradrenaline, adrenaline and isoprenaline on neuromuscular transmission in the rat diaphragm and the influence of adrenergic blocking agents on these actions were investigated.2. The resting membrane potential of the muscle fibre was increased by adrenaline (5 x 10(-6)-10(-5) g/ml.) and isoprenaline (5 x 10(-6) g/ml.) up to 3-4 mV, but noradrenaline (5 x 10(-6)-10(-5) g/ml.) had little effect.3. The amplitude and the half-decay time of the end-plate potential (e.p.p.) were increased by noradrenaline (1 x 10(-6) g/ml.), adrenaline (1 x 10(-7)-10(-5) g/ml.) and isoprenaline (1-5 x 10(-6) g/ml.). The potentiation of the amplitude of the e.p.p. was greater with noradrenaline than with adrenaline and isoprenaline.4. Noradrenaline (5 x 10(-6) g/ml.) increased the frequency of miniature end-plate potentials (m.e.p.p.), but not their amplitude. However, isoprenaline (5 x 10(-6) g/ml.) increased the amplitude of m.e.p.p.s without change in frequency. Adrenaline (5 x 10(-6) g/ml.) increased both frequency and amplitude of m.e.p.p.s.5. Adrenaline (5 x 10(-6) g/ml.) and isoprenaline (5 x 10(-6) g/ml.) increased the input resistance of the muscle membrane. The effect was blocked by the beta-blocker, pronethalol (2 x 10(-6) g/ml.), but not by the alpha-blocker, phentolamine (2 x 10(-6) g/ml.). Noradrenaline did not change the input resistance of the muscle fibre.6. Noradrenaline (5 x 10(-6) g/ml.) and adrenaline (5 x 10(-6) g/ml.) augmented the extracellularly recorded end-plate current (e.p.c.), but they had no effect on the half duration, nor on the action current (a.c.) of the nerve terminal, nor on the synaptic delay. Isoprenaline (5 x 10(-6) g/ml.) had no effect on any of these parameters. The actions of noradrenaline and adrenaline on e.p.c. were abolished by phentolamine (2 x 10(-6) g/ml.), but not by pronethalol (2 x 10(-6) g/ml.).7. Adrenaline (5 x 10(-6) g/ml.) and isoprenaline (5 x 10(-6) g/ml.) enhanced the amplitude of the acetylcholine potential elicited by iontophoretic application of acetylcholine. No such effect was produced by noradrenaline (5 x 10(-6) g/ml.).8. It was concluded that noradrenaline acts on the nerve ending increasing the release of transmitter, and that isoprenaline acts on the post-synaptic membrane enhancing the input resistance, while adrenaline has both presynaptic and post-synaptic actions. The effect on the nerve ending is concerned with the alpha-action, whereas that on post-synaptic membrane with beta-action of the catecholamines.