Modeling Gain and Gradedness of Ca2+ Release in the Functional Unit of the Cardiac Diadic Space

摘要: A model of the functional release unit (FRU) in rat cardiac muscle consisting one dihydropyridine receptor (DHPR) and eight ryanodine (RyR) channels, volume surrounding them, is formulated. It assumed that no spatial [Ca2+] gradients exist this volume, each FRU acts independently. The amenable to systematic parameter studies which dynamics are simulated at channel level using Monte Carlo methods with Ca2+ concentrations by numerical integration a coupled system differential equations. Using stochastic methods, Ca(2+)-induced (CICR) shows both high gain graded robust when parameters varied. For single DHPR opening, resulting RyR flux insensitive open duration, determined principally local sarcoplasmic reticulum (SR) load, consistent experimental data on sparks. In addition, openings effective triggering from adjacent RyRs only duration long SR load high. This indicates relatively low coupling between RyRs, suggests mechanism limits regenerative spread openings. results also suggest adaptation plays an important modulatory role shaping magnitude, but not solely responsible for terminating release. Results obtained gradedness can occur recruitment independent FRUs without requiring within or cross-coupling units.