Modulation of calcium currents via alpha 2-adrenoceptors in embryonic chick sympathetic neurons.
In order to gain insight into the mechanism of the autoinhibition of noradrenaline release, the present study explores the effects of substances acting at various adrenoceptor-subtypes on voltage-activated Ca2+ currents. Experiments were carried out on cultured embryonic chick sympathetic neurons using the patch clamp technique. Ca2+ currents associated with a (fully activating) depolarizing 150 ms voltage step to 0 mV were reduced by noradrenaline and the two alpha 2-adrenoceptor agonists UK 14,304 and clonidine, predominantly during the early phase of activation. We quantified these effects by measuring Ca2+ current amplitudes in the absence and presence of substances 10 ms after the beginning of the depolarization. Noradrenaline effects were maximal at 5 mumol/l, causing a 28% depression of the current. Half-maximal effects (IC50) were apparent at 0.7 mumol/l. UK 14,304 was equipotent to noradrenaline (IC50: 0.5 mumol/l; maximal effect: 26% depression). Clonidine, while active in the same range of concentration (IC50: 0.6 mumol/l), had a smaller maximal effect (20% depression). Methoxamine and isoprenaline, on the other hand, did not significantly reduce the Ca2+ current at 10 mumol/l. The noradrenaline-induced inhibition was attenuated by yohimbine (1 mumol/l). Neither prazosin (1 mumol/l) nor propranolol (1 mumol/l) interfered with the effect of noradrenaline. These results indicate a reduction of Ca2+ influx via alpha 2-adrenoceptors and suggest that the autoreceptor-mediated inhibition of transmitter release in embryonic chick sympathetic neurons operates through the modulation of Ca2+ channels.
Institute of Neuropharmacology, University of Vienna, Austria.
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Boehm
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Huck
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000502:physiology*; D002642:Chick Embryo; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D003000:Clonidine; D002118:Calcium; D009638:Norepinephrine