title: Negative feedback regulation of intracellular Ca2+ and the slope of the dose-response curve.
abstract: Cytosolic calcium ions are known to act as an intracellular messenger. The response of the cell may be governed by a power of the internal Ca2+ concentration. This causes a very steep relationship between concentration and response. Dose-response curves of tissues acted on by external agonists are less steep. A possible explanation for this discrepancy is offered. During steady stimulation, which increases Ca2+ inflow and its cytosolic concentration, mechanisms which counteract the increased level by removing Ca2+ are likely to be activated. If these were stimulated by cytosolic Ca2+, they would constitute a negative feedback. If the removal mechanisms were governed by a power of the cytosolic Ca2+ concentration, the negative feedback would have positive co-operativity. A mathematical model is developed where entry of extracellular Ca2+ results from stimulation while a co-operative extrusion pump provides negative feedback. It is shown that, in the steady state, positive co-operativity in the extrusion pump is able to reduce the steepness of the dose-response curve.
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005246:Feedback; D006801:Humans; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism
chemical_list: D002118:Calcium