JSIM modeling raises questions about calcium‐independent contractions of porcine pulmonary artery (PPA)

Abstract

Vascular smooth muscle uses both extracellular calcium [Ca2+]o and intracellular stores of calcium to signal a strong, sustained contraction. There is also evidence of calcium‐independent regulation. This study investigated the contraction of PPA in the absence of [Ca2+]o with the prediction that high potassium depolarization would induce an increase of intracellular calcium [Ca2+]i from [Ca2+]o and the sarcoplasmic reticulum (SR). When PPA was repeatedly stimulated to contract in 0 [Ca2+]o Krebs solution with EGTA, it was expected that SR calcium would become depleted. Isometric force was measured in isolated PPA tissue, and the resulting rate constants and magnitude of force development were modeled using JSIM Physiome Modeling Software. After repeated contraction in the absence of [Ca2+]o a fast rate process was missing compared to contractions in the presence of [Ca2+]o, but the magnitude of force did not decline. Only the ability to sustain force and to remain relaxed became impaired. Physiome modeling with JSIM will be used to explore alternative contractile mechanisms to explain these results.