title: Functional nonequality of the cardiac and skeletal ryanodine receptors.
abstract: Dihydropyridine receptors (DHPRs), which are voltage-gated Ca2+ channels, and ryanodine receptors (RyRs), which are intracellular Ca2+ release channels, are expressed in diverse cell types, including skeletal and cardiac muscle. In skeletal muscle, there appears to be reciprocal signaling between the skeletal isoforms of both the DHPR and the RyR (RyR-1), such that Ca2+ release activity of RyR-1 is controlled by the DHPR and Ca2+ channel activity of the DHPR is controlled by RyR-1. Dyspedic skeletal muscle cells, which do not express RyR-1, lack excitation-contraction coupling and have an approximately 30-fold reduction in L-type Ca2+ current density. Here we have examined the ability of the predominant cardiac and brain RyR isoform, RyR-2, to substitute for RyR-1 in interacting with the skeletal DHPR. When RyR-2 is expressed in dyspedic muscle cells, it gives rise to spontaneous intracellular Ca2+ oscillations and supports Ca2+ entry-induced Ca2+ release. However, unlike RyR-1, the expressed RyR-2 does not increase the Ca2+ channel activity of the DHPR, nor is the gating of RyR-2 controlled by the skeletal DHPR. Thus, the ability to participate in skeletal-type reciprocal signaling appears to be a unique feature of RyR-1.
authors.affiliation: Department of Information Physiology, National Institute of Physiological Science, Myodaiji-cho, Okazaki, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nakai
authors.forename: T
authors.initials: T
authors.lastname: Ogura
authors.forename: F
authors.initials: F
authors.lastname: Protasi
authors.forename: C
authors.initials: C
authors.lastname: Franzini-Armstrong
authors.forename: P D
authors.initials: PD
authors.lastname: Allen
authors.forename: K G
authors.initials: KG
authors.lastname: Beam
mesh_terms: D000818:Animals; D001921:Brain; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D017629:Gap Junctions / Q000648:ultrastructure; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium