values of 10 nM and 1 ms for the single stimulation and 1 μM and 100 ms for the
long release process. In the single case (and also in the short process), zinc clearance
is mainly due to zinc binding to the NMDA 2A and GLAST sites, while in the long
stimulation, it is essentially mediated by the formation of GLAST complexes. All the
other complexes, characterized by lower affinities, are formed in smaller concentrations, as can be seen in Figures 2 and 3.
An overview of the main results of this study can be observed in Figure 4, for
the single, short, and long processes.
4. Discussion
Mathematical models are a highly valuable tool for the study of synaptic zinc
dynamics and in particular of cleft zinc changes. After release, zinc interacts with a
variety of pre- and postsynaptic mechanisms which, together with uptake, mediate
cleft zinc clearance. In the simpler case, which assumes no postsynaptic zinc entry
as considered in this study, all released zinc returns, after some time, to the presynaptic area.
Previous works have suggested that there is no zinc entry in the postsynaptic
region for concentrations below 10 μM [18, 20, 27, 56]. As previously reported [12],
our model assumes different zinc release events that lead to maximum cleft free
zinc concentrations in the range 10 nM to 1 μM, which are below 10 μM. With these
values, there should be no zinc entering to the postsynaptic area.
The released zinc can form complexes with various synaptic zinc-binding sites
existing mainly on pre- and postsynaptic VDCCs (N- and L-types), K ATP channels,
ionotropic glutamate receptors (AMPA, KA, and NMDA), and also cleft free molecules (ATP) and glial glutamate transporters (EAAT4). The mathematical model
Figure 3.
Zinc complexes for the single and long release processes with time courses similar to those of free zinc. Complexes
with unknown on and off-rate constants, assumed to be always at equilibrium with free zinc, formed with (a)
AMPA receptors (left), N-VDCCs (center), and K ATP channels (right). (b) The same type of complexes formed
with EAAT4 transporters (left), KA receptors (center), and ATP molecules (right). For both the single (smaller
traces) and the long (larger traces) release processes, the signals are displayed by decreasing order of amplitude.
Note the different scales.
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Advances in Neural Signal Processing
long release process. In the single case (and also in the short process), zinc clearance
is mainly due to zinc binding to the NMDA 2A and GLAST sites, while in the long
stimulation, it is essentially mediated by the formation of GLAST complexes. All the
other complexes, characterized by lower affinities, are formed in smaller concentrations, as can be seen in Figures 2 and 3.
An overview of the main results of this study can be observed in Figure 4, for
the single, short, and long processes.
4. Discussion
Mathematical models are a highly valuable tool for the study of synaptic zinc
dynamics and in particular of cleft zinc changes. After release, zinc interacts with a
variety of pre- and postsynaptic mechanisms which, together with uptake, mediate
cleft zinc clearance. In the simpler case, which assumes no postsynaptic zinc entry
as considered in this study, all released zinc returns, after some time, to the presynaptic area.
Previous works have suggested that there is no zinc entry in the postsynaptic
region for concentrations below 10 μM [18, 20, 27, 56]. As previously reported [12],
our model assumes different zinc release events that lead to maximum cleft free
zinc concentrations in the range 10 nM to 1 μM, which are below 10 μM. With these
values, there should be no zinc entering to the postsynaptic area.
The released zinc can form complexes with various synaptic zinc-binding sites
existing mainly on pre- and postsynaptic VDCCs (N- and L-types), K ATP channels,
ionotropic glutamate receptors (AMPA, KA, and NMDA), and also cleft free molecules (ATP) and glial glutamate transporters (EAAT4). The mathematical model
Figure 3.
Zinc complexes for the single and long release processes with time courses similar to those of free zinc. Complexes
with unknown on and off-rate constants, assumed to be always at equilibrium with free zinc, formed with (a)
AMPA receptors (left), N-VDCCs (center), and K ATP channels (right). (b) The same type of complexes formed
with EAAT4 transporters (left), KA receptors (center), and ATP molecules (right). For both the single (smaller
traces) and the long (larger traces) release processes, the signals are displayed by decreasing order of amplitude.
Note the different scales.
120
Advances in Neural Signal Processing