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The process of Ca 2+  release from sarcoplasmic reticulum (SR) comprises 4 phases in smooth muscle cells. Phase 1 is characterized by a large increase of the intracellular Ca 2+  concentration ([Ca 2+ ] i ) with a minimal reduction of the free luminal SR [Ca 2+ ] ([Ca 2+ ] FSR ). Importantly, active SR Ca 2+  ATPases (SERCA pumps) are necessary for phase 1 to occur. This situation cannot be explained by the standard kinetics that involves a fixed amount of luminal Ca 2+  binding sites. A new mathematical model was developed that assumes an increasing SR Ca 2+  buffering capacity in response to an increase of the luminal SR [Ca 2+ ] that is called Kinetics-on-Demand (KonD) model. This approach can explain both phase 1 and the refractory period associated with a recovered [Ca 2+ ] FSR . Additionally, our data suggest that active SERCA pumps are a requisite for KonD to be functional; otherwise luminal SR Ca 2+  binding proteins switch to standard kinetics. The importance of KonD Ca 2+  binding properties is twofold: a more efficient Ca 2+  release process and that [Ca 2+ ] FSR  and Ca 2+ -bound to SR proteins ([Ca 2+ ] BSR ) can be regulated separately allowing for Ca 2+  release to occur (provided by Ca 2+ -bound to luminal Ca 2+  binding proteins) without an initial reduction of the [Ca 2+ ] FSR .

Kinetics on Demand Is a Simple Mathematical Solution that Fits Recorded Caffeine-Induced Luminal SR Ca2+ Changes in Smooth Muscle Cells