INVOLVEMENT OF DIFFERENT TYPES OF VOLTAGE-SENSITIVE CALCIUM CHANNELS IN THE PRESYNAPTIC REGULATION OF NORADRENALINE RELEASE IN RAT-BRAIN CORTEX AND HIPPOCAMPUS

Transmitter release at the nerve terminal is mediated by the influx of Ca2+ through voltage-sensitive calcium channels (VSCCs). Many types o f VSCCs have been found in neurons (T, N, L, and P), but uncertainty r emains about which ones are involved in neuronal excitation-secretion coupling. Specific ligands for the L- and N-type VSCCs were used to de termine which of these subtypes might be involved in the K+-evoked [H- 3]-noradrenaline release from superfused rat brain cortical and hippoc ampal synaptosomes. In cortical presynaptic terminals the 1,4-dihydrop yridine agonist Bay K 8644 enhanced the K+ (15 mM)-evoked [H-3] noradr enaline release. This effect was reversed by the 1,4-dihydropyridine a ntagonists nimodipine and nitrendipine. The L-type VSCC ligands had no effect on hippocampal synaptosomes. In contrast, the N-type VSCC bloc ker omega-conotoxin markedly reduced the K+-evoked [H-3]-noradrenaline release in nerve terminals from both regions. Inhibition was greater in hippocampal synaptosomes. When applied together the inhibitory acti ons of nimodipine and omega-conotoxin were approximately additive. The se findings indicate that both L- and N-type VSCCs participate in nora drenaline release in rat brain cortex and suggest that noradrenergic t erminals in the two regions examined may have distinct populations of VSCCs: L type in cortex and N type in hippocampus.