Neuromuscular transmission and smooth muscle membrane properties in the guinea-pig ear artery

Abstract

Effects of noradrenaline and alpha-adrenoceptor blocking agents on neuromuscular transmission of the guinea-pig ear artery were assessed using the micro-electrode method.1. The mean membrane potential, and length and time constants of the longitudinally oriented muscle cells were -64.5 +/- 5 mV (n = 150), 1.03 +/- 0.16 mm (n = 15) and 410 +/- 40 msec (n = 7) respectively. From the current-voltage relationship, weak outward current pulses produced an anomalous rectification of the membrane while stronger intensities produced a normal rectification of the membrane with a depolarization over 10-15 mV.2. Brief stimulation (0.1-0.5 msec) of the tissue produced an excitatory junction potential (e.j.p.). Facilitation produced by repetitive stimulation was evident only on very rare occasions. Higher stimulus intensities caused a stepwise increase of the amplitude of e.j.p.s.3. Spontaneously generated miniature excitatory junction potentials (m.e.j.p.s) were recorded from the muscle membrane. In many cells, the interval and amplitude histograms of m.e.j.p.s showed skew curves. On rare occasions, a bell-shaped amplitude distribution (quantal release of packeted noradrenaline (NA)) was observed.4. NA (> 3 x 10(-7)m) depolarized the membrane and increased the membrane resistance, as measured from the amplitude of the electrotonic potential. Phentolamine suppressed the NA-induced depolarization. However, high concentrations of phentolamine (> 10(-5)m) depolarized the membrane and increased the membrane resistance.5. NA (10(-8)m) caused no change in membrane potential though it suppressed the amplitude of an e.j.p. produced by a single stimulus, but did not suppress the amplitude of the subsequent e.j.p.s evoked by repetitive stimulation (0.2-2.0 Hz). A higher concentration of NA (3 x 10(-7)m) depolarized the membrane and markedly suppressed the amplitude of e.j.p.s. On the other hand, NA (10(-8) or 2 x 10(-8)m) generated burst discharges of m.e.j.p.s between silent periods or random generation.6. Phentolamine (10(-6)m) markedly enhanced the amplitude of e.j.p.s and caused a smooth facilitation in response to a train of stimuli with no effect on the membrane potential. A stepwise change in the amplitude of e.j.p.s was no longer observed at any given stimulus frequency and intensity.7. Phenoxybenzamine (10(-7)m) suppressed the amplitude of e.j.p.s with no change in the membrane potential.8. The results led to the conclusion that, at a concentration which has no effect on the post-junctional muscle membrane, NA and phentolamine seemed to be more effective on prejunctional adrenoceptors, while phenoxybenzamine seemed to have a greater effect on post-junctional adrenoceptors. NA depresses adrenergic transmission by negative feed-back, while the enhancing action of phentolamine can be explained partly by blocking of prejunctional adrenoceptors and, in addition, by an increase of NA release.