title: Voltage independence of vasomotion in isolated irideal arterioles of the rat.
abstract: The cellular mechanisms underlying vasomotion of irideal arterioles from juvenile rats have been studied using electrophysiological methods, ratiometric calcium measurements and video microscopy. Vasomotion was not affected by removal of the endothelium. Spontaneous contractions were preceded by spontaneous depolarizations. Both were abolished by the intracellular calcium chelator, BAPTA AM (20 microM), but not by ryanodine (10 microM), suggesting a dependence on the cyclical release of calcium from intracellular stores, other than those operated by ryanodine receptors. Oscillations were little changed when the membrane potential of short segments of arteriole was either depolarized or hyperpolarized. When the segments were voltage clamped, oscillating inward currents were recorded, indicating that the changes in membrane potential were voltage independent. Vasomotion was preceded by intracellular calcium oscillations and both were abolished by inhibitors of phospholipase C (U73122, 10 microM), phospholipase A(2) (AACOCF(3), 30 microM) and protein kinase C (chelerythrine chloride, 5 microM, and myristoylated protein kinase C peptide, 10 microM). Inhibition of vasomotion by the dual lipoxygenase and cyclo-oxygenase inhibitor, NDGA (10 microM), the lipoxygenase inhibitor, ETI (1 microM) but not by the cyclo-oxygenase inhibitors, aspirin (10 microM) and indomethacin (10 microM), or the cytochrome P450 inhibitor 17-ODYA (10 microM), suggested an involvement of the lipoxygenase pathway. The observations suggest that vasomotion of iris arterioles is voltage independent and results from the cyclical release of calcium from IP(3)-sensitive stores which are activated by cross talk between the phospholipase C and phospholipase A(2) pathways in vascular smooth muscle.
authors.affiliation: Division of Neuroscience, John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT, 2601, Australia. rebecca.haddock@anu.edu.au
authors.forename: R E
authors.initials: RE
authors.lastname: Haddock
authors.forename: G D S
authors.initials: GD
authors.lastname: Hirst
authors.forename: C E
authors.initials: CE
authors.lastname: Hill
mesh_terms: D000470:Alkaloids; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001160:Arterioles / Q000201:enzymology; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D007498:Iris / Q000098:blood supply*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D018408:Patch-Clamp Techniques; D010507:Periodicity; D010617:Phenanthridines / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000470:Alkaloids; D001095:Arachidonic Acids; D053119:Benzophenanthridines; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D010617:Phenanthridines; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C081565:arachidonyltrifluoromethane; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D012433:Ryanodine; D004533:Egtazic Acid; C016299:chelerythrine; D010741:Phospholipases A; D010738:Type C Phospholipases; D002118:Calcium