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.