An experimental test of a model for repeated Ca2+ spikes in osteoblastic cells.
A model for cytosolic Ca2+ spikes is presented that incorporates continual influx of Ca2+, uptake into an intracellular compartment, and Ca(2+)-induced Ca2+ release from the compartment. Two versions are used. In one, release is controlled by explicit thresholds, while in the other, release is a continuous function of cytosolic and compartmental [Ca2+]. Some model predictions are as follows. Starting with low Ca2+ influx and no spikes: (1) induction of spiking when Ca2+ influx is increased. Starting with spikes: (2) increase in magnitude and decrease in frequency when influx is reduced; (3) inhibition of spiking if influx is greatly reduced; (4) decrease in the root-mean-square value when influx is increased; and (5) elimination of spiking if influx is greatly increased. Since there is good evidence that hyperpolarizing spikes reflect cytosolic Ca2+ spikes, we used electrophysiological measurements to test the model. Each model prediction was confirmed by experiments in which Ca2+ influx was manipulated. However, the original spike activity tended to return within 5-30 min, indicating a cellular resetting process.
Ferrier
J
J
Medical Research Council Group in Periodontal Physiology, University of Toronto, Ont., Canada.
Kesthely
A
A
Lagan
E
E
Richter
C
C
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004553:Electric Conductivity / Q000187:drug effects; D005583:Fourier Analysis; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009543:Nifedipine / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D002118:Calcium