Role of local calcium domains in activation of calcium-induced calcium release in crayfish muscle fibers
Gyorke, S.; Palade, P.
American Journal of Physiology 264(6 Part 1): C1505-C1512
Simultaneous measurements were made of crayfish muscle Ca-2+ currents (I-Ca) and the intracellular Ca-2+ transients they elicit due to Ca-2+-induced Ca-2+ release (CICR) from the sarcoplasmic reticulum (SR). Ca-2+ concentration ((Ca-2+)) elevations produced by Ca-2+ entry via I-Ca were much more effective in triggering CICR than were ongoing release or homogeneous elevations of Ca-2+ produced by photolysis of caged Ca-2+. This suggests that (Ca-2+) gradients exist when Ca-2+ is elevated by I-Ca and that, during Ca-2+ entry, (Ca-2+) at the activation site of the release channels must be much greater than spatially averaged (Ca-2+) reported by the indicator. Analysis of voltage dependencies of I-Ca inactivation and SR Ca-2+ release suggest that both Ca-2+-dependent processes are controlled by I-Ca via the nearest T tubule Ca-2+ channel rather than by total I-Ca entry. The contribution of SR Ca-2+ release to I-Ca inactivation studied with a two-pulse protocol was less than predicted if Ca-2+ derived from SR Ca-2+ release and from T tubule Ca-2+ channels have equal access to the Ca-2+ binding site controlling I-Ca inactivation. These results can be explained in terms of a scheme where sites for release activation and I-Ca inactivation are located in the same junctional gap subdomain, closer to the cytoplasmic mouth of the T tubule Ca-2+ channel than to the cytoplasmic mouth of the SR Ca-2+ release channels. Such a scheme could provide an explanation for the graded nature and selective control of CICR in this preparation as well as in vertebrate cardiac muscle.