Bistability in the Ca(2+)/calmodulin-dependent protein kinase-phosphatase system.
A mathematical model is presented of autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMKII) and its dephosphorylation by a phosphatase. If the total concentration of CaMKII subunits is significantly higher than the phosphatase Michaelis constant, two stable steady states of the CaMKII autophosphorylation can exist in a Ca(2+) concentration range from below the resting value of the intracellular [Ca(2+)] to the threshold concentration for induction of long-term potentiation (LTP). Bistability is a robust phenomenon, it occurs over a wide range of parameters of the model. Ca(2+) transients that switch CaMKII from the low-phosphorylated state to the high-phosphorylated one are in the same range of amplitudes and frequencies as the Ca(2+) transients that induce LTP. These results show that the CaMKII-phosphatase bistability may play an important role in long-term synaptic modifications. They also suggest a plausible explanation for the very high concentrations of CaMKII found in postsynaptic densities of cerebral neurons.
Zhabotinsky
A M
AM
Department of Chemistry and Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110, USA. zhabotinsky@brandeis.edu
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D001921:Brain / Q000201:enzymology; D020013:Calcium Signaling; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013569:Synapses / Q000201:enzymology
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C110531:calmodulin dependent protein kinase II phosphatase; D010749:Phosphoprotein Phosphatases