Type 3 ryanodine receptors of skeletal muscle are segregated in a parajunctional position

Abstract

A key event in skeletal muscle activation is the rapid release of Ca 2؉ from the sarcoplasmic reticulum (SR), the Ca 2؉ storage organelle in the muscle cell. The surface membrane͞transverse tubules and the SR form functional units (calcium release units containing one or two couplons or junctions), where the voltage-sensing dihydropyridine receptor of the surface membrane interacts with the SR Ca 2؉ release channel [ryanodine receptor (RyR)] and depolarization of the cell membrane is converted into Ca 2؉ release from the SR. Although RyR1 is the most important isoform in skeletal muscle, some muscles also express high levels of RyR3, an isoform with a wide tissue distribution. The cytoplasmic domains of RyRs are visible in the electron microscope as periodically disposed feet. We find that, in muscles containing only RyR1, feet are exclusively located over the junctional SR surface facing the surface membrane͞transverse tubule. In muscles containing RyR1 as well as RyR3, additional feet are located in lateral parajunctional regions immediately adjacent to junctional SR. Biochemical content of RyR3 and content of parajunctional feet are highly correlated in different muscles and the disposition of parajunctional versus junctional feet are notably different. On the basis of these two observations, we postulate that RyR3s are restricted to the parajunctional region, and thus their activation must be indirect and derivative during excitation-contraction coupling.

Calcium-Induced Calcium Release in Skeletal Muscle

“…These results might be consistent with the notion that CICR participates in physiological Ca 2ϩ release, especially because Ca , the characteristic distance that a Ca 2ϩ is expected to diffuse before being captured by a Ca buffer (192), is calculated to be less than ϳ30 nm at fura 2 concentrations greater than 3-4 mM (115), which coincides with the 28 nm separating junctional and parajunctional rows of RyR (64). Yet, such a conclusion must be made with caution, as these authors pointed out that the results may also be due to the pharmacological effects of a high concentration of fura 2 unrelated to complexation with Ca 2ϩ , because 1) with higher concentrations of fura 2, the initial rising phase of Ca 2ϩ release is much slower than that in control, which should not occur if the effect of fura 2 is only the result of complexation with Ca 2ϩ to reduce secondary CICR (116), and 2) the inhibitory effect of higher concentrations of fura 2 on Ca 2ϩ release takes minutes to develop, whereas the result of complexation with Ca 2ϩ should appear immediately (115).…”

“…The coordination might involve coupled gating (163) between RyR1 channels associated with DHPR tetrads and unassociated channels. However, coupled gating is believed to be unlikely in the case of RyR3 or RyR␤ on morphological grounds (64). CICR is unlikely to be the mechanism of coordination because its P o is too low to support the reliable production of Ca 2ϩ sparks.…”

“…The theory was further elaborated to a proposed model assuming release generators, couplons, composed of equal numbers of voltage-gated channels and Ca 2ϩ -gated channels interacting through the local Ca 2ϩ concentration (253). Later, Felder and FranziniArmstrong (64) showed that the foot structures lacking t-tubule voltage sensors at the t-SR junctional region are also RyR1 or RyR␣ and that RyR3 and RyR␤ are located at lateral parajunctional regions immediately adjacent to the junctional region. However, the essential point in the model is that at least half of RyRs, RyR␤, are not associated with t-tubule voltage sensors but are located at a position close to the voltage sensor-associated RyR␣, and that point is not altered.…”

Skeletal muscle calcium channel ryanodine and the development of pale, soft, and exudative meat in poultry

“…-induced Ca 2+ -release mechanism (Felder and Franzini-Armstrong, 2002). For βRYR in species that possess this Ca 2+ channel in skeletal muscle in the same proportion as the αRYR located in a parajunctional region immediately adjacent to the SR junctional region, βRYR activation would be indirect during the excitation-contraction event (Murayama and Kurebayashi, 2011).…”

Optical single-channel resolution imaging of the ryanodine receptor distribution in rat cardiac myocytes

“…Given the highly ordered double-row structure seen in skeletal muscle (26), it is possible that RyR clusters are assembled onto a structural template. The approximately exponential size distribution seen here, however, argues against the idea that RyR cluster size is very tightly controlled.…”