Alpha‐drenergic inhibition of calcium‐dependent potentials in rat sympathetic neurones.

Abstract

Post-ganglionic neurons of the rat superior cervical ganglion were studied in vitro (21-26.degree. C) using single intracellular micro-electrode methods. Three Ca2+-dependent potentials were studied: the shoulder on the normal action potential, the hyperpolarizing afterpotential (h.a.p.) and the Ca2+ spike. Bath-applied noradrenaline [norepinephrine] reversibly inhibited these Ca2+-dependent potentials. The EC50 for inhibition of peak h.a.p. amplitude was about 1 .mu.M. The order of catecholamine potency was: L-adrenaline [epinephrine] > L-noradrenaline > D-noradrenaline .simeq. dopamine > DL-isoprenaline. Phentolamine (10 .mu.M), an .alpha.-blocker, but not MJ-1999 [4-[1-hydroxy-2''-[isopropylamino]ethyl]methanesulfonanilide hydrochloride] (10 .mu.M), a .beta.-blocker, antagonized the action of noradrenaline. Noradrenaline (10 .mu.M) hyperpolarized most neurons (1-6 mV), with no detectable change in resting membrane conductance. Superfusion with low external Ca2+ and high Mg2+ mimicked the effect of noradrenaline. Either procedure alone antagonized the h.a.p. conductance increase but did not alter the h.a.p. reversal potential. However, in the presence of low Ca2+, high Mg2+, the remaining action potential and h.a.p. were not further reduced by noradrenaline. The Ca2+-dependent shoulder of the action potential appeared dependent on GK [K conductance]. Noradrenaline and low Ca2+ antagonized the shoulder when enhanced by TEA+ or Ba2+. The rate of rise and amplitude of the Ca2+ spike were antagonized by noradrenaline. Activation of an .alpha.-adrenoceptor apparently inhibits a voltage-sensitive Ca2+ conductance (GCa(V)), reducing the inward Ca2+ current which may generate the normal action potential shoulder and the rising phase of the Ca2+ spike. Reduction of Ca2+ current reduces the Ca2+-dependent portion of outward K+ current underlying the h.a.p.