An Electrophysiological Analysis of the Effects of Morphine on the Calcium Dependence of Neuromuscular Transmission in the Mouse Vas Deferens

Abstract

1 The effects of morphine on the Ca-dependence of the synaptic potential amplitude in the mouse vas deferens have been determined.2 The synaptic potential increased with a power factor of 2.4 for [Ca]. between 0.7 mm and 1.8 mm.Morphine (40 nM) decreased the synaptic potential, without altering the second power relationship between the synaptic potential and [Ca]0. 3 Morphine reversed the depression in the synaptic potential which develops during a short highfrequency (10 Hz) train of impulses to facilitation. Consequently the synaptic potential beyond the tenth impulse was unaffected by morphine. 4 Morphine did not alter the facilitation of the synaptic potential which develops during a short low-frequency (<2 Hz) train of impulses in normal [Ca]0. Consequently morphine decreased the synaptic potential for each impulse by about the same percentage amount. 5 Morphine increased the small facilitation in the synaptic potential which occurs during a short low-frequency (< 2 Hz) train of impulses in high [Ca]0. This facilitation approximated the predictions based on the assumption that each impulse leaves residual Ca ions bound to receptors involved in transmitter release from the nerve terminal.

The dependence of excitatory junction potential amplitude on the external calcium concentration in narcotic tolerant mouse vas deferens

“…Addition of The 2.4 power relationship between [Ca]. and noradrenaline release observed in these studies confirms the findings of others (Bennett & Florin, 1975;Bennett & Lavidis, 1980;Milner et al, 1982) and possi- (Bennett & Florin, 1975) using the mass action law derived by Jenkinson (1957 mesenteric ganglion (Bornstein & Fields, 1979) nor with morphine; (0) chronic morphine-treated (CMT) in the smooth muscle cells of vasa deferentia (North (Bennett & Lavidis, 1980;Illes etal., 1980). These possibilities are supported by the finding that acute administration of morphine in mice and rats decreases Ca2+ levels in synaptosomes and in synaptic vesicles (Harris et al, 1977;Yamamoto et al, 1978).…”

“…Facilitation oftransmifer release during lowfrequency stimulation in vasa deferentia from tolerant mice During a low frequency train of impulses the amount of transmitter released by successive impulses has been shown to be facilitated, and the degree of facilitation is calcium-dependent (Bennett & Fisher, 1977;Bennett & Lavidis, 1980). Smith & Zucker (1980) have shown that there is no facilitation of the entry of calcium into the terminal during a train of impulses but there is a prolonged rise in the internal calcium concentration.…”

“…This reduction is reversed either by increasing extracellular calcium, by reducing the extracellular magnesium, or by naloxone (Bennett & Lavidis, 1980;Illes et al, 1980). The action of morphine on the release site during trains of impulses can be explained as follows: by reducing the number of Ca-X that are formed, the amount of noradrenaline released by the first impulse in the train is reduced (Bennett & Lavidis, 1980). This results in an increase in the Ca-receptors free to bind to calcium entering the terminal with subsequent impulses and therefore facilitation is enhanced.…”

“…Acute administration of morphine to isolated tissues results in a reduction of transmitter release from nerve terminals during electrical stimulation (Paton, 1957;Schaumann, 1957;Henderson et al, 1975;Bornstein & Fields, 1979;Bennett & Lavidis, 1980). In the inferior mesenteric ganglion, the morphineinduced depression of the amplitude of the synaptic potential has been shown to be due entirely to a reduction in the number of quanta released rather than a decrease in quantal size and, although the spontaneous quantal release frequency is depressed by morphine (Bornstein & Fields, 1979), the size of spontaneously released quanta is unaltered (Bornstein & Fields, 1979; lUes .…”

“…Mudge et al, (1979) showed that the voltage dependent calcium current produced during stimulation of cultured dorsal root ganglion cells is shortened by enkephalin and that this effect is reversed by naloxone. It is likely therefore, that the morphine-induced inhibition of the evoked release of noradrenaline from the mouse vas deferens is mediated via an inhibition of the voltage-dependent calcium channels directly or indirectly by a K+mediated hyperpolarization of the terminal (Morita & North, 1982) or by preventing the association of calcium to an intracellular X-receptor involved in transmitter release (Bennett & Lavidis, 1980;Illes et al, 1980). The development of tolerance to opiates is well documented and can be measured either in vivo or in vitro.…”