The diversity of alpha(2) and purinergic autoreceptor actions on action potential evoked calcium transients in single varicosities has been investigated using the calcium indicator Oregon Green 488 BAPTA-1. 2. During long trains of impulses (10 Hz for 30 s), the change in calcium concentration in varicosities from its resting level (DeltaCa(2+)) increased in many varicosities during the first 3 s of stimulation before reaching a plateau. 3. The alpha(2) adrenoceptor agonist clonidine (1 microM) decreased DeltaCa(2+) by over 40% during short trains (five impulses at 5 Hz) in most varicosities, although some were unaffected. The alpha(2) adrenoceptor antagonist idazoxan (2 microM) increased the DeltaCa(2+) plateau following long trains in most varicosities. Hence, most varicosities possess alpha(2) adrenoceptors which are activated when noradrenaline accumulates extracellularly. 4. During long trains of impulses, the P(2y)-purinergic receptor agonist 2-methyl-thio-ATP (100 microM) decreased DeltaCa(2+) plateau by about 50% in most varicosities; alpha,beta-methylene ATP (100 microM) decreased it by about 50% in a minority of varicosities; adenosine (200 microM) had no significant effect. Suramin (100 microM) increased the DeltaCa(2+) during all stimulus protocols in most varicosities, suggesting that ambient ATP modulates DeltaCa(2+) responses. The P(2y) receptor antagonist reactive blue (100 microM) affected a minority of varicosities. Given that most varicosities respond to suramin, other P(2) receptor subtypes are probably present. 5. The ATP ectoenzyme antagonist ARL67157 (50 microM) decreased the plateau DeltaCa(2+) during long trains in complete strings of varicosities but not in others. 6. The present technique indicates that varicosities have diverse autoreceptor utilization.
