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

1. Post‐ganglionic neurones of the rat superior cervical ganglion were studied in vitro (21‐26 degrees C) using single intracellular micro‐electrode methods. 2. Three Ca2+‐dependent potentials were studied: the shoulder on the normal action potential, the hyperpolarizing afterpotential (h.a.p.), and th Ca2+ spike. 3. Bath‐applied noradrenaline reversibly inhibited these Ca2+‐dependent potentials. The EC50 for inhibition of peak h.a.p. amplitude was about 1 microM. The order of catetholamine potency was: L‐adrenaline > L‐noradrenaline > D‐noradrenaline congruent to dopamine > DL‐isoprenaline. Phentolamine (10 microM), an alpha‐blocker, but not MJ‐1999 (10 microM), a beta‐blocker, antagonized the action of noradrenaline. 4. Noradrenaline (10 microM) hyperpolarized most neurones (1‐6 mV) studied, with no detectable change in resting membrane conductance. 5. 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. 6. The Ca2+‐dependent shoulder of the action potential did not appear dependent upon GK. Noradrenaline and low Ca2+ antagonized the shoulder when enhanced by TEA+ or Ba2+. 7. Both the rate of rise and amplitude of the Ca2+ spike were antagonized by noradrenaline. 8. We propose that activation of an alpha‐adrenoceptor inhibits a voltage‐sensitive Ca2+ conductance (GCa(V)), thereby reducing the inward Ca2+ current which may generate the noraml action potential shoulder and the rising phase of the Ca2+ spike. Reduction of Ca2+ current would also reduce the Ca2+‐dependent portion of outward K+ current underlying the h.a.p.