The diffusion of Ca as it converges to the external mouth of a Ca
channel is examined. Diffusional limitation on Ca ions entering Ca
channels during current flow, cause local extracellular Ca depletions.
Such extracellular Ca depletions have been reported in cardiac muscle.
The cardiac sarcolemma has a large number of low-affinity Ca binding
sites that can buffer these local Ca depletions. For a hemisphere
of extracellular space (of radius less than 0.33 microns) centered
on the external mouth of a Ca channel the amount of Ca bound at the
membrane surface exceeds that which is free within the associated
hemisphere. The ratio of bound Ca/free Ca increases as r decreases,
such that the Ca nearest the Ca channel is the most strongly buffered
by sarcolemmal bound Ca. It is demonstrated that Ca ions coming from
these sarcolemmal Ca binding sites contribute quantitatively to the
integrated Ca current. The electric field generated by the local
depletion of Ca near the channel mouth has little impact on the extent
of Ca depletion, but if an additional electric field exists at the
mouth of the channel, Ca depletion can be significantly altered.
Other low-affinity Ca binding sites in the interstitium may also
contribute to the buffering of extracellular Ca. The complex geometry
of the extracellular space in cardiac muscle (e.g., transverse tubules
and restrictions of extracellular space between cells) increases
both the predicted Ca depletions (in the absence of binding) and
the bound/free ratio. Thus, the impact of this surface Ca binding
is greatly increased. By considering arrays of Ca channels in transverse
tubules or in parallel planes (e.g., membranes of neighboring cells),
extracellular Ca depletions are predicted which agree with those
measured experimentally. Membrane Ca binding may also be expected
to buffer increases in Ca around the inner mouth of Ca channels.
It is demonstrated that in the absence of other intracellular systems
most of the Ca entering the cell via Ca channels might be expected
to be bound to the inner sarcolemmal surface. It is concluded that
surface Ca binding may have a substantial impact on the processes
of extracellular Ca depletion (and intracellular Ca accumulation).