Diffusion around a cardiac calcium channel and the role of surface bound calcium

Abstract

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).