Characterization of α₂-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones

Intracellular recordings were made from locus coeruleus neurones in a slice of rat pons superfused in vitro. A single-electrode voltage-clamp amplifier was used to measure membrane currents. Superfusion of the slice with clonidine (3-100nM) or noradrenaline (100nM-100μM), or brief application of noradrenaline from a pipette by a pressure pulse, caused dose-dependent membrane hyperpolarizations. Phenylephrine (10 μM) and isoprenaline (10 μM) were ineffective. The hyperpolarizations were accompanied by a decrease in neurone input resistance. The hyperpolarization evoked by pressure ejection of noradrenaline could be reversed by membrane polarization to -110 mV. Clonidine and noradrenaline caused a membrane current which was linearly related to membrane potential between -50 and -120mV, being outward at resting levels and reversing at -110mV. The concentration-response curves for clonidine and noradrenaline were shifted rightwards in a parallel manner by α₂-adrenoceptor antagonists. The antagonist K_es estimated from the degree of shift were: RX 781094 9nM, yohimbine 14 nM, phentolamine 20 nM and piperoxane 49 nM. These experiments indicate that in locus coeruleus neurones an increase in potassium conductance results from activation of α₂-adrenoceptors similar to those characterized on peripheral neurones.