Ca2+ sequestration as a determinant of chaos and mixed-mode dynamics in agonist-induced vasomotion.
We have investigated the contribution of smooth muscle Ca2+ stores to chaotic vasomotion in isolated rabbit ear resistance arteries. In preparations constricted by histamine, exposure to cyclopiazonic acid (CPA) and thapsigargin (TSG), which inhibit the Ca2+-adenosinetriphosphatase (ATPase) pump of the sarcoplasmic reticulum, first induced then abolished highly characteristic mixed-mode oscillatory behavior. The fractal dimension of the vasomotion, which reflects the minimum number of contributing dynamic variables, remained between 2 and 4 until the point at which oscillations disappeared completely. By contrast, ryanodine, which attenuates Ca2+-induced Ca2+ release, decreased the fractal dimension of the responses to <2 in a graded concentration-dependent fashion by selectively suppressing a slow subcomponent of the overall rhythmic activity. CPA-associated oscillations were insensitive to ryanodine but could be abolished by verapamil and modulated in an inhibitory or stimulatory fashion by charybdotoxin, which blocks Ca2+-activated K+ channels, and by ouabain, which blocks the Na+-K+-ATPase. We conclude that there is nonlinear cross talk between CPA/TSG-sensitive Ca2+ stores and a membrane oscillator that regulates Ca2+ influx and that the kinetics of Ca2+ uptake by the CPA/TSG-sensitive pool can be distinguished dynamically from the kinetics of Ca2+ release from its ryanodine-sensitive subcomponent.
Griffith
T M
TM
Department of Diagnostic Radiology, University of Wales College of Medicine, Cardiff, United Kingdom.
Edwards
D H
DH
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D018999:Charybdotoxin / Q000494:pharmacology; D004423:Ear / Q000098:blood supply; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D017711:Nonlinear Dynamics; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D018999:Charybdotoxin; D012433:Ryanodine; D010042:Ouabain; D019284:Thapsigargin; D006632:Histamine; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; C000543:cyclopiazonic acid