Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A program of physical activity for people over 60 yr of age was developed to determine whether exercising at lower intensities (LI) is a significant conditioning stimulus. In addition, differences in aerobic capacities (VO2max) elicited by training at LI, as opposed to training at higher intensities (HI), were evaluated. Thirty-two volunteers over 60 yr of age (mean = 67.8 yr) participated in a 9-wk exercise program. After initial testing of VO2max on a cycle ergometer, subjects were assigned randomly to the HI, LI, or control group. Endurance training of the two exercise groups on cycle ergometers was maintained at 30-45% (N = 14) or 60-75% (N = 14) of the range (HRR) between the subject's resting and maximum heart rate for 25 min during each exercise session. These training intensities represented 57 and 70% of the VO2max of the LI and HI groups, respectively. Participants averaged three exercise sessions per week. Non-exercising volunteers served as control subjects. A one-way ANOVA with repeated measures was utilized for comparisons of retest, groups, and interaction. As a result of the exercise program, significant changes (P less than 0.005) in absolute (VO2max, 1 X min-1) and relative (VO2max, ml X min-1 X kg-1) aerobic capacities were realized within each training group while initial and post-training VO2max were not significantly different between the two groups. Similar changes were documented by a reduction in heart rate at submaximal exercise intensities and during recovery. It was concluded that exercising at LI (30-45% HRR) is an adequate training stimulus in older individuals and produces changes in VO2max that are comparable to those elicited by HI (60-75% HRR) training.
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PMID:Physiological adjustments to higher- or lower-intensity exercise in elders. 665 59

Functional studies on vascular smooth muscle suggest the presence of ryanodine receptors (RyRs) with differing properties. In an attempt to understand such differences we investigated, using reverse transcription-polymerase chain reaction (RT-PCR), the possibility that smooth muscle cells express multiple types of RyRs. RNA was extracted from rat aorta, superior and small mesenteric arterial vessels, purified aortic smooth muscle media, or cultured aortic smooth muscle cells for cDNA synthesis. The cDNAs encoding RyR1, RyR2, and RyR3 were amplified using PCR primers based on sequences close to the 3' coding region of the RyR genes and PCR products verified by restriction endonuclease analysis. All three members of the RyR gene family were found to be present in vascular smooth muscle. This finding of multiple types of RyRs expressed in the same cell type indicates a complex mechanism of RyR Ca2+ channel regulation involving the formation of homo- and/or heterotetrameric complexes.
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PMID:Multiple types of ryanodine receptor/Ca2+ release channels are expressed in vascular smooth muscle. 748 46

We have used [3H]ryanodine binding experiments and single channel recordings to provide convergent descriptions of the effect of imperatoxin A (IpTxa), a approximately 5-kDa peptide from the venom of the scorpion Pandinus imperator (Valdivia, H. H., Kirby, M. S., Lederer, W. J., and Coronado, R. (1992) Proc. Ntl. Acad. Sc. U.S.A. 89, 12185-12189) on Ca2+ release channels/ryanodine receptors (RyR) of sarcoplasmic reticulum (SR). At nanomolar concentrations, IpTxa increased the binding of [3H]ryanodine to skeletal SR and, to a lesser extent, to cerebellum microsomes. The activating effect of IpTxa on skeletal SR was Ca(2+)-dependent, synergized by caffeine, and independent of other modulators of RyRs. However, IpTxa had negligible effects on tissues where the expression of skeletal-type RyR isoforms (RyR1) is small or altogether absent, i.e. cardiac, cerebrum, and liver microsomes. Thus, IpTxa may be used as a ligand capable of discriminating between RyR isoforms with nanomolar affinity. IpTxa increased the open probability (Po) of rabbit skeletal muscle RyRs by increasing the frequency of open events and decreasing the duration of the closed lifetimes. This activating effect was dose-dependent (ED50 = 10 nM), had a fast onset, and was fully reversible. Purified RyR from solubilized skeletal SR displayed high affinity for [3H]ryanodine with a KD of 6.1 nM and Bmax of approximately 30 pmol/mg of protein. IpTxa increased [3H]ryanodine binding noncompetitively by increasing Bmax to approximately 60 pmol/mg of protein. These results suggested the presence of an IpTxa-binding site on the RyR or a closely associated regulatory protein. This site appears to be distinct from the caffeine- and adenine nucleotide-regulatory sites. IpTxa may prove a useful tool to identify regulatory domains critical for channel gating and to dissect the contribution of skeletal-type RyRs to intracellular Ca2+ waveforms generated by stimulation of different RyR isoforms.
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PMID:Peptide probe of ryanodine receptor function. Imperatoxin A, a peptide from the venom of the scorpion Pandinus imperator, selectively activates skeletal-type ryanodine receptor isoforms. 749 90

Contraction of skeletal muscle is triggered by the release of Ca2+ from the sarcoplasmic reticulum (SR) after depolarization of transverse tubules. The ryanodine receptor exists as a 'foot' protein in the junctional gap between the sarcoplasmic reticulum and the transverse tubule in skeletal muscle, and is proposed to function as a calcium-release channel during excitation-contraction (E-C) coupling. Previous complementary DNA-cloning studies have defined three distinct subtypes of the ryanodine receptor in mammalian tissues, namely skeletal muscle, cardiac and brain types. We report here mice with a targeted mutation in the skeletal muscle ryanodine receptor gene. Mice homozygous for the mutation die perinatally with gross abnormalities of the skeletal muscle. The contractile response to electrical stimulation under physiological conditions is totally abolished in the mutant muscle, although ryanodine receptors other than the skeletal-muscle type seem to exist because the response to caffeine is retained. Our results show that the skeletal muscle ryanodine receptor is essential for both muscular maturation and E-C coupling, and also imply that the function of the skeletal muscle ryanodine receptor during E-C coupling cannot be substituted by other subtypes of the receptor.
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PMID:Excitation-contraction uncoupling and muscular degeneration in mice lacking functional skeletal muscle ryanodine-receptor gene. 751 81

Microsomal sarcoplasmic reticulum (SR) fractions from lobster skeletal muscle were found to bind [3H]-ryanodine. [3H]-ryanodine binding was enhanced by AMP, Ca2+ and caffeine, and significantly diminished by ATP, Ba2+ and Sr2+. Furthermore, dantrolene and ruthenium red, two classical inhibitors of Ca2+ release from the SR, blocked [3H]-ryanodine binding. Similarly, tetracaine, known to block the charge movement associated with excitation-contraction coupling in vertebrate muscle, inhibited the binding of the alkaloid. Our lobster SR preparation exhibited a single high-affinity ryanodine binding site (Kd = 6.6 nM, Bmax = 10 pmol/mg protein). Since SDS-PAGE of the SR proteins revealed a major band c. 565 kDa which comigrated with the putative ryanodine receptor from both rat and chicken skeletal muscle, we concluded that lobster skeletal muscle is equipped with the 565 kDa ryanodine receptor. Finally, incorporation of the SR microsomal fraction from lobster into planar bilayer membranes revealed the presence of a ryanodine-sensitive Ca2+ channel activity (160 pS in symmetrical 200 mM CsCl solutions). We concluded that both the crustacean and vertebrate skeletal muscle ryanodine receptor share the relevant properties such as molecular weight and affinity for ryanodine and inositol 1,4,5 triphosphate. However, there are important differences between the two receptors including differential effects of the alkaloid on the Ca2+ release channel and modulation of the receptor by nucleotides.
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PMID:Properties of the ryanodine receptor present in the sarcoplasmic reticulum from lobster skeletal muscle. 751 63

cDNAs encoding trpE fusion proteins containing fragments of the skeletal muscle Ca2+ release channel (ryanodine receptor) were expressed in bacteria. The fusion proteins, which covered about 90% of the linear sequence of the ryanodine receptor, were used to identify calmodulin- (CaM), Ca(2+)-, and ruthenium red-binding regions in the ryanodine receptor through the use of 125I-CaM, 45Ca2+, and ruthenium red overlay procedures. Six Ca(2+)-dependent CaM-binding domains were detected in the skeletal muscle ryanodine receptor. Strong CaM-binding domains were localized in regions 6, 11, 12, and 13, in subregions 6b, 11b, and 13b, and in short sequences 6b3, 11b1, and 13b2, lying between amino acid residues 2063 and 2091, 3611 and 3642, and 4303 and 4328. Weaker CaM-binding domains were localized in regions 4, 9, and 10 and in subregions 4b, 9b, and 10a, lying between residues 921 and 1173, 2804 and 2930, and 2961 and 3084. Most of these CaM-binding domains encompassed all or part of previously predicted CaM-binding sites. Strong 45Ca(2+)- and ruthenium red-binding sites domains were localized in the NH2- and COOH-terminal regions of the ryanodine receptor and in regions 6, 12, and 13. The 45Ca(2+- and ruthenium red-binding sites in regions 6 and 12 were localized in subregions 6b and 12b, lying between residues 1861-2094 and 3657-3776. These data together with earlier studies (Chen, S. R. W., Zhang, L., and MacLennan, D. H. (1992) J. Biol. Chem. 267, 23318-23326), show that strong CaM-, Ca(2+)-, and ruthenium red-binding domains are colocalized in the skeletal muscle ryanodine receptor.
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PMID:Identification of calmodulin-, Ca(2+)-, and ruthenium red-binding domains in the Ca2+ release channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum. 752 30

Anaesthesia-induced malignant hyperthermia (MH) may be caused by specific gene defects in the skeletal muscle ryanodine receptor. We have studied the frequency of occurrence of the C1840T mutation, analogous to the porcine mutation, and three mutations associated both with MH and central core disease (G7301A, C487T and C1209G). We investigated skeletal muscle specimens from up to 137 patients testing negative and 101 patients testing positive for MH susceptibility by the North American MH Group protocol. The presence or absence of the mutations was determined by polymerase chain reaction and restriction enzyme digestion. The frequencies of occurrence of the C1840T and C487T mutations were 2% and 1%, respectively, in MH-positive subjects and were the only two mutations identified. One subject with central core disease did not have any of the three mutations examined associated with this disorder. Therefore, the porcine and central core disease-associated mutations examined in the ryanodine receptor account for a small proportion (approximately 3%) of MH-positive diagnoses. The mutations examined did not occur in any of the MH-negative patients, supporting an association between defects in the ryanodine receptor and a positive diagnosis for MH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genotype and phenotype relationships for mutations in the ryanodine receptor in patients referred for diagnosis of malignant hyperthermia. 754 49

Ryanodine receptor (RyR) is a calcium release channel protein on the intracellular Ca(2+)-store. While inositol 1,4,5-trisphosphate receptor (IP3R), another intracellular calcium release channel protein, is mainly found in non-muscle cells, such as neurons and hepatocytes, and smooth muscles, RyR is the Ca(2+)-release channel protein in skeletal and cardiac muscles. At least three genetically distinct isoforms of RyR are identified: isoform proteins Ryr1, Ryr2, and Ryr3 expressed by ryr1, ryr2 and ryr3, respectively. In the central nervous system where IP3R is much more abundant than RyR, the main isoform of RyR is Ryr2, which is specific to the cardiac ventricular muscle. Recently, ryr3 was detected in specific regions of the brain. In this paper, the heterogeneous distribution and localization of RyR isoforms in the brain are summarized. The discussion extends into their putative functions, especially potential involvement in neuronal plasticity.
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PMID:[Ryanodine receptors in the central nervous system]. 755 30

Recent advances in determining the three-dimensional architecture of the skeletal muscle ryanodine receptor/calcium release channel (RyR) by cryo-electron microscopy and three-dimensional reconstruction are discussed. The tetrameric receptor is characterized by a large 4-fold symmetric cytoplasmic assembly that consists of many domains separated by solvent-containing crevices and holes. Experimental evidence suggests that at least one regulatory ligand, calmodulin, binds to sites on the cytoplasmic assembly that are at least 10 nanometers from the transmembrane channel.
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PMID:Three-dimensional architecture of the skeletal muscle ryanodine receptor. 764 82

Deprivation of vitamin A (retinol) leads to reduced potential of B cell proliferation and nearly complete block of T cell activation in vitro. Retinol, which is thought to function as a pro-hormone, is enzymatically converted into intracellular messenger molecules. Thus, 14-hydroxy-retro-retinol (14-HRR) is an intracellular messenger molecule linked to activation and growth regulation of lymphocytes; whereas, anhydroretinol, another natural retro-retinoid, is an antagonist of 14-HRR effects. In this article, we describe the isolation, structure determination, synthesis, and biological properties of a new intracellular retinol derivative, 13,14-dihydroxy-retinol (DHR), which also supports the viability of retinol-deprived lymphocytes. DHR is found in numerous cell lines representing a large cross-section of tissues and animals from insects to mammals. In T lymphocytes the production of DHR and 14-HRR is up-regulated by phorbol ester. DHR is converted to 14-HRR by mild acid treatment, but not by cells; therefore DHR is not a biosynthetic intermediate in the conversion of retinol to 14-HRR. DHR is a distinct end point of retinol metabolism. Although it is linked to cell proliferation, its biological role remains to be determined.
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PMID:13,14-Dihydroxy-retinol, a new bioactive retinol metabolite. 764 43


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