AHEART September 46/

Parthimos, D., D. H. Edwards, and T. M. Griffith. Minimal model of arterial chaos generated by coupled intracellular and membrane Ca21 oscillators. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1119–H1144, 1999.—We have developed a mathematical model of arterial vasomotion in which irregular rhythmic activity is generated by the nonlinear interaction of intracellular and membrane oscillators that depend on cyclic release of Ca21 from internal stores and cyclic influx of extracellular Ca21, respectively. Four key control variables were selected on the basis of the pharmacological characteristics of histamine-induced vasomotion in rabbit ear arteries: Ca21 concentration in the cytosol, Ca21 concentration in ryanodine-sensitive stores, cell membrane potential, and the open state probability of Ca21-activated K1 channels. Although not represented by independent dynamic variables, the model also incorporates Na1/Ca21 exchange, the Na1-K1-ATPase, Cl2 fluxes, and Ca21 efflux via the extrusion ATPase. Simulations reproduce a wide spectrum of experimental observations, including 1) the effects of interventions that modulate the functionality of Ca21 stores and membrane ion channels, 2) paradoxes such as the apparently unpredictable dual action of Ca21 antagonists and low extracellular Na1 concentration, which can abolish vasomotion or promote the appearance of large-amplitude oscillations, and 3) period-doubling, quasiperiodic, and intermittent routes to chaos. Nonlinearity is essential to explain these diverse patterns of experimental vascular response.