Abstract
The function of calcium entry or release channels is often modulated
by the cytosolic free calcium concentration. When such channels are
studied in isolation, calcium buffer solutions are usually used to
control the free calcium at the cytosolic face of the channel. Such
solutions are generally formulated on the basis of equilibrium considerations.
We calculate the gradient of Ca$^2+$ in the vicinity of a channel
pore, in the presence of such buffers. We find that the effective
degree of buffering near the pore is markedly affected by kinetic
considerations. Commonly used EGTA solutions are completely ineffective
in buffering Ca$^2+$ within macromolecular distances of the
pore. In order to achieve useful buffering, the fastest buffers (e.g.
BAPTA derivatives) must be used, in concentrations very much higher
than those conventionally employed. Because of the diffusion limit
on the maximum rate of binding of calcium to the buffer ligand, it
is physically impossible to achieve good control of Ca$^2+$
at cytosolic levels at distances of less than a few nm from a pore
conducting pico-ampere calcium current.
- 1315621
- animal
- animals,
- atpase,
- benzofurans,
- biological,
- buffers,
- calcium
- calcium,
- calibration,
- cardiovascular,
- cell
- cells,
- channels,
- comparative
- concentration,
- contraction,
- cultured,
- cyclic,
- cytosol,
- dietary
- diffusion,
- digestion,
- dismutase,
- dyes,
- esterification,
- ethers,
- extracellular
- feed,
- female,
- fish
- fluorescent
- gov't,
- growth
- heart,
- hormone,
- human
- hydrogen-ion
- hypoxia,
- in
- inbred
- indoles,
- ischemia,
- kinetics,
- lactation,
- mathematics,
- membrane
- mitochondria,
- models,
- myocardial
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