Adaptive control of intracellular Ca2+ release in C2C12 mouse myotubes.

Laser scanning confocal imaging was used to monitor release of Ca2+ from localized regions in a skeletal muscle cell line with sparsely distributed Ca2+ release sites. The goal was to distinguish between two schemes proposed to explain the phenomenon of "quantal" Ca2+ release from caffeine-sensitive Ca2+ stores in muscle and other tissues: (1) all-or-none (true quantal) Ca2+ release from functionally discrete stores that have different sensitivities to caffeine; or (2) adaptive behavior of individual release sites, each responding transiently and repeatedly to incremental caffeine doses. Our results showed that Ca2+ release induced by K+ or caffeine occurs in discrete loci within the cell. The image areas and fluorescence intensities of some of these evoked local signals were similar to those of Ca2+ sparks that were observed under resting conditions and which are believed to be due to spontaneous activation of single release units. In contrast to the expectations imposed by quantal models, incremental doses of caffeine activated the same sets of release sites throughout the cell. Ca2+ release, at a given site, triggered by a submaximal dose of caffeine was transient and could be reactivated by addition of a higher caffeine dose, showing the same type of adaptive behavior as measured globally from larger areas of the cell. These results suggest that incremental Ca2+ release is accounted for by adaptive behavior of individual Ca2+ release sites.