Bistability in the Ca2+/calmodulin-dependent protein kinase-phosphatase system
                                          Zhabotinsky AM
                                     BIOPHYSICAL JOURNAL
                                     79 (5): 2211-2221 NOV 2000
Abstract:
A mathematical model is presented of autophosphorylation of Ca2+/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 Ca2+ concentration range from
below the resting value of the intracellular [Ca2+] 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. Ca2+ 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
Ca2+ 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.