Calcium Mobilization and Spontaneous Transient Outward Current Characteristics upon Agonist Activation of P2Y2 Receptors in Smooth Muscle Cells

Abstract

A quantitative model is provided that links the process of metabotropic receptor activation and sequestration to the generation of inositol 1,4,5-trisphosphate, the subsequent release of calcium from the central sarcoplasmic reticulum, and the consequent release of calcium from subsarcolemma sarcoplasmic reticulum that acts on large-conductance potassium channels to generate spontaneous transient outward currents (STOCs). This model is applied to the case of STOC generation in vascular A7r5 smooth muscle cells that have been transfected with a chimera of the P2Y2 metabotropic receptor and green fluorescent protein (P2Y2-GFP) and exposed to the P2Y2 receptor agonist uridine 5′-triphosphate. The extent of P2Y2-GFP sequestration from the membrane on exposure to uridine 5′-triphosphate, the ensuing changes in cytosolic calcium concentration, as well as the interval between STOCs that are subsequently generated, are used to determine parameter values in the model. With these values, the model gives a good quantitative prediction of the dynamic changes in STOC amplitude observed upon activation of metabotropic P2Y2 receptors in the vascular smooth muscle cell line.