Coupled Gating Between Individual Skeletal Muscle Ca ²⁺ Release Channels (Ryanodine Receptors)

Abstract

Excitation-contraction coupling in skeletal muscle requires the release of intracellular calcium ions (Ca2+) through ryanodine receptor (RyR1) channels in the sarcoplasmic reticulum. Half of the RyR1 channels are activated by voltage-dependent Ca2+ channels in the plasma membrane. In planar lipid bilayers, RyR1 channels exhibited simultaneous openings and closings, termed "coupled gating." Addition of the channel accessory protein FKBP12 induced coupled gating, and removal of FKBP12 uncoupled channels. Coupled gating provides a mechanism by which RyR1 channels that are not associated with voltage-dependent Ca2+ channels can be regulated.

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

“…Thus, it is expected that RyR3 activation is a secondary event in e-c coupling, and that it follows the primary activation of RyR1 by DHPR (34), resulting in its amplification. Parajunctional feet do not seem to be in a close contact with junctional feet, which would exclude functional pairing between parajunctional RyR3 and junctional RyR1, of the type suggested for RyR1 by Marx et al (35). The most likely possibility is that RyR3 are activated by the wave of Ca 2ϩ resulting from opening of RyR1 (7,34,36,37).…”

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

“…Under physiological conditions (i.e., the absence of immunosuppressive drugs), FKBPs are though to bind to RyRs with high affinity and stabilize the closed state of the channel (Ahern et al 1994;Brillantes et al 1994;McCall et al 1996;Ahern et al 1997;Marx et al 1998;Marx et al 2001). Removal of FKBP12, by preventing rebinding with an immunosuppressive drug or as the result of a genetic FKBP deficiency leads to greater open probability of the channel and longer mean open times (Ahern et al 1997;Marx et al 1998;Shou et al 1998). Furthermore, FKBP12 displacement in skeletal muscle alters the coupling between RyR1 and Ca V 1.1.…”

The quantal nature of Ca 2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells

“…This pattern of RyRC organization seems to be highly conserved from crustaceans to vertebrates (13,15,16), suggesting that array formation is critical to RyRC-mediated Ca 2ϩ signaling in vivo. Thus, understanding array-based RyRC behavior is of fundamental importance for elucidation of intracellular Ca 2ϩ signaling mechanism.Despite a wealth of information on behavior of RyRCs in planar lipid bilayers and other cell-free systems (5,(17)(18)(19)(20), little is known on how RyRCs operate in situ; many fundamental issues regarding the genesis and termination of Ca 2ϩ sparks remain unanswered (5,21,22). Based on in vitro properties of RyRCs, the classic Ca 2ϩ -induced Ca 2ϩ release (CICR) mechanism (23) would predict an all-or-none activation of the RyRC array and an everlasting local Ca 2ϩ release, which cannot explain the prompt termination of Ca 2ϩ sparks and the microstability of intracellular signaling (24, 25).…”

“…Despite a wealth of information on behavior of RyRCs in planar lipid bilayers and other cell-free systems (5,(17)(18)(19)(20), little is known on how RyRCs operate in situ; many fundamental issues regarding the genesis and termination of Ca 2ϩ sparks remain unanswered (5,21,22). Based on in vitro properties of RyRCs, the classic Ca 2ϩ -induced Ca 2ϩ release (CICR) mechanism (23) would predict an all-or-none activation of the RyRC array and an everlasting local Ca 2ϩ release, which cannot explain the prompt termination of Ca 2ϩ sparks and the microstability of intracellular signaling (24,25).…”