Modulation of calcium currents via α₂-adrenoceptors in embryonic chick sympathetic neurons

Summary

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 Ca ²⁺ 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 a2-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 µmol/l, causing a 28% depression of the current. Half-maximal effects (IC₅₀) were apparent at 0.7 µmol/l. UK 14,304 was equipotent to noradrenaline (IC₅₀: 0.5 µmol/l; maximal effect: 26% depression). Clonidine, while active in the same range of concentration (IC₅₀: 0.6 µmol/l), had a smaller maximal effect (20% depression). Methoxamine and isoprenaline, on the other hand, did not significantly reduce the Ca ²⁺ current at 10 µmol/l. The noradrenaline-induced inhibition was attenuated by yohimbine (1 µmol/I). Neither prazosin (1 µmol/l) nor propranolol (1 µmol/l) interfered with the effect of noradrenaline.

These results indicate a reduction of Ca ²⁺ influx via α₂-adrenoceptors and suggest that the autoreceptor-mediated inhibition of transmitter release in embryonic chick sympathetic neurons operates through the modulation of Ca²⁺ channels.