Abstract
The excitatory junction current (EJC) evoked by electrical stimulation of postganglionic sympathetic nerves of rat tail artery with 100 pulses at 2 Hz, at 1.3 mmol/l external Ca2+, was used as a measure of the per pulse release of ATP. In controls the EJCs were initially facilitated, then gradually depressed during the stimulus train. The first EJC was slightly depressed by the α2-adrenoceptor antagonist yohimbine, but starting from the 4th pulse the EJCs were enhanced. Yohimbine increased the early facilitation without markedly modifying the subsequent depression. The yohimbine-induced enhancement of EJCs caused by pulses 11–100 was, thus, constant. The noradrenaline reuptake blocker cocaine depressed the EJCs, abolished the early facilitation and slightly enhanced the depression. These effects of cocaine were reversed by further addition of yohimbine. The α2-adrenoceptor agonist xylazine (1 and 10 μmol/1) dose dependently depressed the EJCs starting from the first pulse. The inhibitory effect of 1 μmol/l xylazine, but not that of 10 μmol/l xylazine, declined with train length.
The inhibition of individual EJCs caused by activation of presynaptic α2-adrenoceptors was used to monitor the concentration of released noradrenaline at these receptors. The ratio of individual EJCs in the presence and absence of yohimbine was assumed to reflect, pulse by pulse, the relative concentration of released noradrenaline at the presynaptic α2-adrenoceptors, and hence termed [NA]α 2. For comparison, the concentration of endogenous noradrenaline was monitored electrochemically by differential pulse amperometry with a carbon fibre microelectrode; this signal is termed [NA]CF. [NA]α 2 and [NA]CF grew during the first 7 – 10 or 14 – 16 pulses, respectively, and then remained relatively constant throughout the stimulus train. Cocaine caused [NA]α 2 and [NA]CF to continue to grow during the first 35 and 50 pulses, and enhanced their peak levels by 180% and 320%, respectively. For comparison with the effects on the EJCs mediated via presynaptic α2-adrenoceptors, those caused by varying external Ca2+ level were examined. At 0.65 mmol/1 Ca2+ the amplitude of the first EJC was smaller than that at 1.3 mmol/1 Ca2+, but the facilitation of later EJCs was enhanced and the subsequent depression reduced. An increase in external Ca2+ to 2.6 mmol/1 had the opposite effects. All effects on EJCs caused by changes in external Ca2+ were maximal for the first EJC and then declined with train length.
The results show (i) that changes in the amplitude of individual EJCs during a 2 Hz train, caused by activation of presynaptic α2-adrenoceptors, may by used to monitor pulse by pulse the concentration of neurally released noradrenaline at these receptors ([NA]α 2), (ii) that [NA]α 2 grows during the first ten pulses to a plateau which is maintained until the end of the stimulus train, (iii) that an exogenous α2-adrenoceptor agonist or changes in the external Ca2+ concentration affect the release probability in all varicosities uniformly, (iv) that activation of presynaptic α2-adrenoceptors by released endogenous noradrenaline preferentially inhibits release from ‘weak’ varicosities while ‘strong’ varicosities were immune, and (iv) that the degree of activation of these receptors controls the per pulse release, and thereby the level of the [NA]α 2 plateau at steady state.
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Msghina, M., Gonon, F. & Stjarne, L. A novel electrophysiological approach to monitor pulse by pulse the concentration of released noradrenaline at the presynaptic α2-adrenoceptors of sympathetic nerves in rat tail artery. Naunyn-Schmiedeberg's Arch Pharmacol 351, 173–185 (1995). https://doi.org/10.1007/BF00169331
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DOI: https://doi.org/10.1007/BF00169331