Biomedical Engineering Reference
In-Depth Information
There are several common features that play a role in cellular calcium signaling
(
Figure 3.1
).
These include calcium influx across the plasma membrane through
calcium channels (
J
influx
), calcium efflux across the plasma membrane (
J
efflux
)
via calcium pumps (
J
PMCA
), and exchangers (
J
NaCa
), release from intracellular
calcium stores (
J
release
) via either ryanodine receptors (
J
RyR
) or IP3 receptors
(
J
IP3R
), sequestrations of calcium by internal stores (
J
uptake
or
J
SERCA
), calcium
binding proteins (
J
buffer
), mitochondrial calcium handling (
J
mito
) by the uniporter
(
J
uni
)andNa
+
-Ca
2
+
exchange (
J
NaCaX
), and diffusion of calcium (
J
diffusion
).
The change of calcium concentration with respect to time is simply a sum of the
fluxes that arise from these features
d
[
Ca
i
]
dt
=
J
diffusion
(3.1)
To correctly describe cellular calcium dynamics, biophysically accurate mathe-
matical representations for the above are needed. This chapter will first describe
these common features of calcium signaling and their mathematical representation.
Moreover, specific examples of how the cellular microscopic ultrastructure provides
a framework in which these components can yield complex behaviors.
J
influx
+
J
efflux
+
J
release
+
J
uptake
+
J
buffer
+
J
mito
+
3.2 Basic principles
Calcium Buffering
Calcium is maintained at a very low level in resting cells. This is due in part to
the presence of calcium buffers that bind approximately 90-99% of the total calcium
found in the cytosol. These buffers are typically calcium binding proteins, such as
calbindin, calretinin, calmodulin, calsequestrin, calcineurin and parvalbumin, or the
negative charges associated with the cellular membranes [25, 47]. These buffers
are quite fast so that they have the effect of binding almost all the calcium that enters
cytosol. This has the effect of reducing the amplitude of changes in cytosolic calcium
concentration.
Another effect of calcium buffers is its effect on calcium mobility. While the
majority of calcium buffers are stationary or fixed to an immobile component of the
cell, there are also mobile buffers that diffuse throughout the cytoplasm. Calcium
indicator dyes are typically mobile buffers (exogenous buffers). Due to the high
concentration of calcium buffers, a calcium ion can only diffuse a short distance
before being immobilized by binding to a calcium buffer. The net effect is that
the effective diffusion constant of calcium in the cytoplasm is 36 n
m
2
/s while the
calcium diffusion constant in cytoplasmic extracts is 223 n
m
2
/s [2]. This reduction
in calcium mobility by calcium buffers has to be included in any realistic model of
spatial calcium signaling.
The reaction of calcium (Ca) binding to a buffer (B) can be described as a chemical
Search WWH ::
Custom Search