Modelling Neuronal Calcium Dynamics - Computational Neuroscience: A Comprehensive Approach - page 84

calcium.

3.3.1 Local domain calcium

Local calcium domains have been demonstrated to be crucial to neuronal function.
For example, the secretion of neurotransmitter in nerve terminal is critically depen-
dent on the activation of specific voltage gated calcium channels, but not on release
from internal stores [4, 5]. In PC 12 cells (rat pheochromocytoma cells), calcium
entry across the plasma membrane through voltage gated channels is essential the
secretion of catecholamines [3]. Calcium release from internal stores does not trig-
ger secretion of catecholamines even in the presence of membrane depolarization in
calcium free medium. This suggests that the elevation of calcium close to the plasma
membrane calcium channels is essential for secretion.
The requirement of calcium entry might also depend on the specific voltage gated
calcium channels involved. In mouse or neonatal rat motor nerve terminals, exper-
iments have indicated that neurotransmitter release is activated by the opening of
P/Q-type calcium channels but not by either L- or N-type calcium channels [42, 52].
Not only is calcium necessary for synaptic vesicle release, there is also evidence
that elevated calcium in the nerve terminals is also necessary for the synaptic vesicle
endocytosis also [11].
To model this, one must consider local domains of elevated calcium ( Figure 3.4) .
In the discussion above, the vesicles respond to calcium local to specific voltage
gated calcium channels in the plasma membrane. Bulk elevations of calcium do
not activate vesicle exocytosis, but the high local calcium that occurs during plasma
membrane voltage gated channels does. This suggests voltage gated channels are in
close proximity to the vesicles as depicted in the figure as P/Q type channels. Other
voltage gated channel types (N-type) or release from internal stores is more distant
and does not activate vesicle fusion.
This has been modeled by Bertram and co-workers [7]. In their model, they ex-
plored the effect of overlapping calcium microdomains in activating vesicle fusion.
They used a deterministic set of reaction-diffusion equations to describe the sys-
tem. They concluded that calcium current cooperativity increases with the number
of channels in the release site. Furthermore, they found that this increase is much
less than the increase in the number of channels, giving an upper bound on the in-
crease in cooperativity. Another interesting prediction was that the calcium channel
cooperativity was an increasing function of channel distance.
Another model describing transmitter release in the mammalian CNS was pro-
posed by Meinrenken and co-workers [33]. In this work, the effect of the spatial
distribution of clusters of voltage-gated calcium channels on vesicle release was ex-
plored. In this model, vesicles at different locations are exposed to different calcium
concentrations resulting in different release probabilities. The authors suggest that
this spatially heterogeneous release probability has functional advantages for synap-
tic transmission.
A third model of calcium dynamics in the synapse of the frog saccular hair cell
has been proposed by Roberts [40, 41]. In this model, an array of calcium channels