Our previous studies have demonstrated that an increase in intracellular levels of Ca(2+) in neurons is an important component of both the antinociception produced by morphine and morphine's tolerance. The present study tested the hypothesis that the Ca(2+) signaling second messenger, cyclic ADP-ribose (cADPR), derived from CD38 activation participates in morphine antinociception and tolerance....

Schneider (1999) recently addressed the question of whether Ca 2 1 sparks arise from the opening of a single ryanodine receptor (RyR) channel or the simultaneous opening of several channels. The discussion highlighted the importance of single RyR channel permeation and gating in the interpretation of Ca 2 1 spark data. The Schneider (1999) perspective inspired us to extend this theoretical disc...

It is widely accepted that Ca2+ is released from the sarcoplasmic reticulum by a specialized type of calcium channel, i.e., ryanodine receptor, by the process of Ca2+-induced Ca2+ release. This process is triggered mainly by dihydropyridine receptors, i.e., L-type (long lasting) calcium channels, directly or indirectly interacting with ryanodine receptor. In addition, multiple endogenous and ex...

The review examines the relationship between the structure of several ryanodine analogs and (A) binding, (B) channel conductance, and (C) ligand binding kinetics. Comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) are used to quantitatively assign structural correlations. Hydrogen bond donating (but not accepting) ability was found to be highly c...

Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The ne...

Ryanodine receptor 1 (RyR1, the sarcoplasmic reticulum Ca(2+) release channel) and alpha(1S)dihydropyridine receptor (DHPR, the surface membrane voltage sensor) of skeletal muscle belong to separate membrane systems but are functionally and structurally linked. Four alpha(1S)DHPRs associated with the four identical subunits of a RyR form a tetrad. We treated skeletal muscle cell lines with ryan...

Activation of the cardiac ryanodine receptor (RyR2) by Ca(2)+ is an essential step in excitation-contraction coupling in heart muscle. However, little is known about the molecular basis of activation of RyR2 by Ca(2)+. In this study, we investigated the role in Ca(2)+ sensing of the conserved glutamate 3987 located in the predicted transmembrane segment M2 of the mouse RyR2. Single point mutati...

In the sarcoplasmic reticulum membrane of skeletal muscle, the ryanodine receptor forms an aqueous pore identified as the calcium-release pathway that operates during excitation-contraction coupling. The purified ryanodine receptor channel has now been shown to have four properties usually associated with gap junction channels: (i) a large nonspecific voltage-dependent conductance consisting of...

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with substantial morbidity and mortality. It causes profound changes in sarcoplasmic reticulum (SR) Ca2+ homeostasis, including ryanodine receptor channel dysfunction and diastolic SR Ca2+ leak, which might contribute to both decreased contractile function and increased propensity to atrial arrhythmias. In this rev...

Skeletal (RyR1) and cardiac muscle (RyR2) isoforms of ryanodine receptor calcium channels are inhibited by millimollar Ca(2+), but the affinity of RyR2 for inhibitory Ca(2+) is ~10 times lower than that of RyR1. Previous studies demonstrated that the C-terminal quarter of RyR has critical domain(s) for Ca(2+) inactivation. To obtain further insights into the molecular basis of regulation of RyR...