Nitric oxide and arachidonic acid modulation of calcium currents in postganglionic neurones 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 microM) reduced the transient calcium current (ICa) on average by 31% and the sustained ICa 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 microM) reduced the transient ICa on average by 28% and the sustained ICa by 22% and these effects were prevented by the presence of the NO-synthase competitive blocker NG-nitro-L-arginine methylester (L-NAME; 100 microM) in the bathing solution. 4. Arachidonic acid (50 microM) reduced the transient ICa on average by 28% and the sustained ICa by 33%. When added together, arachidonic acid (50 microM) and L-arginine (270 microM) produced the same effects as arachidonic acid alone. 5. Blocking the conversion of arachidonic acid to prostaglandins by addition of indomethacin (20 microM) to the bathing solution did not prevent the depression of either the transient or the sustained calcium current during application of arachidonic acid (50 microM). The effects of arachidonic acid were also not occluded by L-NAME (100 microM) when present in the bathing solution. 6. Inhibiting the biosynthesis of leukotrienes by applying L-663,536 (MK-886; 3 microM) to the bathing solution prevented the depression of both components of ICa during application of arachidonic acid (50 microM). 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.
Khurana
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Physiology Department, University of Sydney, N.S.W. Australia.
Bennett
M R
MR
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001338:Autonomic Fibers, Postganglionic / Q000187:drug effects / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D020024:Leukotriene Antagonists; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D002722:Chlorobenzenes
D016718:Arachidonic Acid; D001120:Arginine; D015220:Calcium Channels; D007211:Indoles; D007213:Indomethacin; D020024:Leukotriene Antagonists; D009569:Nitric Oxide; D019335:Nitroarginine; D009599:Nitroprusside; C060893:MK-886; D002722:Chlorobenzenes