Subtype specificity of the ryanodine receptor for Ca2+ signal amplification in excitation-contraction coupling
Yamazawa, T.; Takeshima, H.; Sakurai, T.; Endo, M.; Iino, M.
EMBO Journal 15(22): 6172-6177
1996
ISSN/ISBN: 0261-4189 PMID: 8947039 Document Number: 464467
In excitable cells membrane depolarization is translated into intracellular Ca-2+ signals. The ryanodine receptor (RyR) amplifies the Ca-2+ signal by releasing Ca-2+ from the intracellular Ca-2+ store upon receipt of a message from the dihydropyridine receptor (DHPR) on the plasma membrane in striated muscle. There are two distinct mechanisms for the amplification of Ca-2+ signalling. In cardiac cells depolarization-dependent Ca-2+ influx through DHPR triggers Ca-2+-induced Ca-2+ release via RyR, while in skeletal muscle cells a voltage-induced change in DHPR is thought to be mechanically transmitted, without a requirement for Ca-2+ influx, to RyR to cause it to open. In expression experiments using mutant skeletal myocytes lacking an intrinsic subtype of RyR (RyR-1), we demonstrate that RyR-1, but not the cardiac subtype (RyR-2), is capable of supporting skeletal muscle-type coupling. Furthermore, when RyR-2 was expressed in skeletal myocytes, we observed depolarization-independent spontaneous Ca-2+ waves and oscillations, which suggests that RvR-2 is prone to regenerative Ca-2+ release responses. These results demonstrate functional diversity among RyR subtypes and indicate that the subtype of RyR is the key to Ca-2+ signal amplification.