Inhibition of Ca‐spikes in rat preganglionic cervical sympathetic nerves by sympathomimetic amines

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Abstract
1 Propagated Ca-spikes were recorded from isolated cervical sympathetic nerve trunks of the rat when bathed in a solution containing 5mM Ca2+, 0.5 or 1 μm tetrodotoxin (to block Na currents) and 1 mM 4-aminopyridine (to reduce K currents). 2 Spikes persisted when external Ca2+ was replaced with Sr2+ or Ba2+, but were blocked by the addition of the following inorganic Ca-channel blockers (in descending order of potency): Cd2+ > La3+ > Ni2+ > Co2+ > Mn2+ > Mg2+. 3 Ca-spike amplitude was reduced by up to 90% by (−)-noradrenaline (IC50 1.5μm). The following sympathomimetic amines imitated this effect (in descending order of potency): clonidine ≥ (−)-adrenaline ≥ [(−)-noradrenaline] ≥ dopamine > (−)-phenylephrine ≥ (±)-amidephrine. 4 Ca-spike inhibition by (−)-noradrenaline was antagonized by phentolamine (pA2 6.5). Yohimbine was about 10 times weaker than phentolamine; (±)-propranolol (1 μm) and prazosin (10 μm) had no clear effect. 5 (−)-Noradrenaline reduced the amplitude of the compound action potential recorded from the superior cervical sympathetic ganglion following supramaximal preganglionic trunk stimulation when recorded in normal Krebs solution and hyperpolarized the ganglion with respect to the postganglionic trunk. Depression of the transmitted ganglionic action potential was antagonized by phentolamine (5 μm) but not by yohimbine (1 μm); in contrast 1 μm yohimbine completely prevented the ganglionic hyperpolarization. (−)-Noradrenaline did not hyperpolarize the preganglionic cervical sympathetic nerve trunk under these recording conditions. 6 It is suggested that inhibition of transmitter release from sympathetic preganglionic fibres produced by noradrenaline results from a depression of the voltage-gated Ca current in the fibres and/or their terminals, and that this action is mediated by an a-adrenoceptor which does not fully conform to either α1 or α2 subtypes.