NITRIC-OXIDE AND ARACHIDONIC-ACID MODULATION OF CALCIUM CURRENTS IN POSTGANGLIONIC NEURONS OF AVIAN CULTURED CILIARY GANGLIA

1 A study has been made of the modulation of high-voltage activated transient and sustained calcium currents in cultured neurones of avian ciliary ganglia by nitric oxide (NO) and arachidonic acid. 2 Sodium nitroprusside (100 muM) reduced the transient calcium current (I(Ca)) on average by 31% and the sustained I(Ca) by 32% during a test depolarization to + 20 mV from a holding potential of - 100 mV. This reduction was maintained for at least 30 min following a single application of sodium nitroprusside. 3 L-Arginine (270 muM) reduced the transient I(Ca) on average by 28% and the sustained I(Ca) by 22% and these effects were prevented by the presence of the NO-synthase competitive blocker N(G)-nitro-L-arginine methylester (L-NAME; 100 muM) in the bathing solution. 4 Arachidonic acid (50 muM) reduced the transient I(Ca) on average by 28% and the sustained I(Ca) by 33%. When added together, arachidonic acid (50 muM) and L-arginine (270 muM) produced the same effects as arachidonic acid alone. 5 Blocking the conversion of arachidonic acid to prostaglandins by addition of indomethacin (20 muM) to the bathing solution did not prevent the depression of either the transient or the sustained calcium current during application of arachidonic acid (50 muM). The effects of arachidonic acid were also not occluded by L-NAME (100 muM) when present in the bathing solution. 6 Inhibiting the biosynthesis of leukotrienes by applying L-663,536 (MK-886; 3 muM) to the bathing solution prevented the depression of both components of I(Ca) during application of arachidonic acid (50 muM). 7 These results indicate that endogenous NO and arachidonic acid pathways are present in parasympathetic ciliary neurones, and that both act to depress high-voltage, gated, calcium channel activity. Nitric oxide; arachidonic acid; calcium current; postganglionic neurones; avian ciliary ganglia