title: Modeling of transcellular Ca transport in rat duodenum points to coexistence of two mechanisms of apical entry.
abstract: Employing realistic parameters, we have demonstrated that a relatively simple mathematical model can reproduce key features of steady-state Ca2+ transport with the assumption of two mechanisms of Ca2+ entry: a channel-like flux and a carrier-mediated transport. At low luminal [Ca2+] (1-5 mM), facilitated entry dominates and saturates with Km = 0.4 mM. At luminal [Ca2+] of tens of millimolar, apical permeability is dominated by the channel flux that in turn is regulated by cytosolic Ca2+. The model reproduces the linear relationship between maximum Ca2+ transport rate and intestinal calbindin D9K (CaBP) content. At luminal [Ca2+] > 50 mM, local sensitivity analysis shows transcellular transport to be most sensitive to variations in CaBP. At low luminal [Ca2+], transport becomes sensitive to apical entry regulation. The simulations have been run within the Virtual Cell modeling environment, yielding the time course of external Ca2+ and spatiotemporal distributions of both intracellular Ca2+ and CaBP. Coexistence of two apical entry mechanisms accords with the properties of the duodenal Ca2+ transport protein CaT1 and the epithelial Ca2+ channel ECaC.
authors.affiliation: Department of Physiology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Slepchenko
authors.forename: F
authors.initials: F
authors.lastname: Bronner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D016764:Cell Polarity; D004386:Duodenum / Q000378:metabolism*; D017136:Ion Transport; D008954:Models, Biological; D051381:Rats; D014807:Vitamin D / Q000494:pharmacology
chemical_list: D014807:Vitamin D; D002118:Calcium