The cardiac sarcoplasmic reticulum calcium-release channel: modulation of ryanodine binding and single-channel activity

Holmberg, Stephen; Williams, Alan J.

doi:10.1016/0005-2736(90)90113-3

Cited by 64 publications

(46 citation statements)

References 29 publications

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“…(Chu et al, 1990;Antaramián et al, 2001). In agreement with results from vertebrate type 1, 2 and 3 RyRs (Antaramián et al, 2001;Zarka and Shashan-Barmatz, 1993;Manunta et al, 2000;Holmberg and Williams, 1990), AMP-PCP (1 mM) promoted a significant increment in [ 3 H]-ryanodine binding (8.6 times over control). Caffeine (10 mM) enhanced [ 3 H]-ryanodine binding in low (10 nM) free Ca 2+ , consistent with vertebrate results (Fig.…”

Section: Database Searchessupporting

confidence: 89%

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Biochemical characterization, distribution and phylogenetic analysis ofDrosophila melanogasterryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase

Vázquez‐Martínez

Cañedo-Merino

Dı́az-Muñoz

et al. 2003

Journal of Cell Science

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IntroductionIntracellular Ca 2+ dynamics is a key factor in cellular signaling and physiology (for a review, see Bootman et al., 2001). In particular, the system of endomembranes that forms the sarco(endo)plasmic reticulum plays a vital role in Ca 2+ handling in most eukaryots (Carafoli and Klee, 1999). In this compartment two families of intracellular Ca 2+ release channels have been characterized: the ryanodine receptors (RyR) and the inositol 1,4,5-trisphosphate receptors (IP3R) (Nori et al., 1993). Besides these, there is evidence for two more intracellular Ca 2+ releasing channels: the NAAPD and the sphingolipid receptors (Petersen and Cancela, 1999;Cancela, 2001). Ca 2+ re-uptake by the sarco(endo)plasmic reticulum is mediated by the thapsigargin-sensitive sarco(endo)plasmic reticulum Ca 2+ ATPase (SERCA), whose structure and function has been studied extensively in mammalian muscle systems (MacLennan, 1990).The development of the fruit fly Drosophila melanogaster is amenable to multidisciplinary analyses (for a review, see Campos-Ortega and Hartenstein, 1997) and is thus a powerful system in which to examine the role of these proteins in intracellular Ca 2+ homeostasis. In this organism, a single RyR gene with 26 exons, dry, and a single IP3R gene with 12 exons, dip, exist and have been genetically characterized (Takeshima et al., 1994;Sinha and Hasan, 1999). In contrast, RyR and IP3R in vertebrates are coded by at least three different genes that, due to alternative splicing, present a large number of isoforms (Rubtsov and Batrukova, 1997;Marks, 1997). A similar situation occurs with the thapsigargin-sensitive Ca 2+ ATPase. In D. melanogaster only one gene coding for this P-type ATPase has been detected, CaP60A (Magyar et al., 1995); whereas in vertebrates, at least three different isoforms of this Ca 2+ ATPase have been reported (Misquitta et al., 1999).Despite extensive genetic and molecular biology data for these proteins, there is a dearth of basic biochemical information on the Drosophila RyR, IP3R and SERCA proteins. In order to reap the benefit from a genetic and molecular biology tractable model organism with single RyR, IP 3 R and SERCA proteins, we characterize here these important molecules using Drosophila native endomembranes.

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Section: Database Searchessupporting

confidence: 89%

“…Type 1 and 3 RyRs are more prone to respond to AMP-PCP than type 2 RyRs (Antaramián et al, 2001;Zarka and ShashanBarmatz, 1993;Manunta et al, 2000;Holmberg and Williams, 1990). Thus, the large Drosophila RyR activation promoted by 1 mM AMP-PCP (Fig.…”

Section: Discussionmentioning

confidence: 94%

Biochemical characterization, distribution and phylogenetic analysis ofDrosophila melanogasterryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase

Vázquez‐Martínez

Cañedo-Merino

Dı́az-Muñoz

et al. 2003

Journal of Cell Science

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“…Caffeine and Ryanodine Response of HEK293 Cells Expressing the wt and Mutant RyR2-Since the high affinity ryanodine binding site is only available when the RyR channel is in an open conformation (16,(33)(34)(35), the profound reduction in [ 3 H]ryanodine binding to some TM10 mutants could indicate that these mutations yield channels that do not open under the conditions used in our binding experiments. In other words, the mutant channel, although readily expressed, is not a functional Ca 2ϩ release channel.…”

Section: Effect Of Mutations In the Tm10 Segment On [ 3 H]ryanodinementioning

confidence: 99%

Residue Gln4863 within a Predicted Transmembrane Sequence of the Ca2+ Release Channel (Ryanodine Receptor) Is Critical for Ryanodine Interaction

Wang

Zhang

Bolstad

et al. 2003

Journal of Biological Chemistry

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Despite the pivotal role of ryanodine in ryanodine receptor (RyR) research, the molecular basis of ryanodine-RyR interaction remains largely undefined. We investigated the role of the proposed transmembrane helix TM10 in ryanodine interaction and channel function. Each amino acid residue within the TM10 sequence, 4844 2؉ . Interestingly these two groups of mutants, each with similar properties, are largely located on opposite sides of the predicted TM10 helix. Single channel analyses revealed that mutation Q4863A dramatically altered the kinetics and apparent affinity of ryanodine interaction with single RyR2 channels and abolished the effect of ryanodol, an analogue of ryanodine, whereas the single channel conductance of the Q4863A mutant and its responses to caffeine, ATP, and Mg 2؉ were comparable to those of the wild type channels. Furthermore the effect of ryanodine on single Q4863A mutant channels was influenced by the transmembrane holding potential. Together these results suggest that the TM10 sequence and in particular the Q4863 residue constitute an important determinant of ryanodine interaction.Ryanodine receptors (RyRs) 1 are a family of intracellular Ca 2ϩ release channels located in the sarco(endo)plasmic reticulum of a variety of cells. They play an essential role in various cellular functions including excitation-contraction coupling, fertilization, and apoptosis (1-7). Three RyR isoforms, RyR1, RyR2, and RyR3, are expressed in mammalian tissues. Mutations in the RyR1 gene have been linked to two human diseases, malignant hyperthermia and central core disease (8 -10), while mutations in the RyR2 genes are associated with polymorphic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy type 2 (11, 12). To understand the impact of the disease-causing mutations and hence the molecular and cellular basis of the diseases, detailed knowledge of the structure-function relationships of RyRs is required.One of the most widely used probes for studying the structure and function of RyRs is ryanodine, a plant alkaloid. The high affinity and specificity of the interaction of ryanodine with RyRs has facilitated the identification, purification, and cloning of the channel (2-5). Ryanodine has also been used to investigate the structural changes associated with channel gating and the mechanisms of ion conduction. Large ryanodineinduced conformational changes in the three-dimensional structure of RyR, in particular in the cytoplasmic assembly, have been observed (13). By monitoring the actions of ryanodine on single RyR channels it has been established that this ligand causes profound alterations in channel function. Interactions of ryanodine with a high affinity site on the channel induce the occurrence of a reduced conductance state with increased open probability, producing an overall effect of channel activation. In the presence of high micromolar to millimolar concentrations of ryanodine the RyR channel closes (5,14).While the functional effects of ryanodine have been well characte...

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“…The binding protocol was a modification of one described previously. 14 Cardiac homogenate proteins (230 g) were incubated for 60 minutes at 37°C with 0.1 to 50 nmol/L [9,21(n)- ] (10 -1 mmol/L) that gave the highest B max in preliminary experiments. Nonspecific binding was determined in the presence of a 1000-fold excess of unlabeled ryanodine (Sigma).…”

Section: Ryanodine Binding Studiesmentioning

confidence: 99%

Right Ventricular Hypertrophy Secondary to Pulmonary Hypertension Is Linked to Rat Chromosome 17

et al. 2001

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Background-Fischer 344 (F344) rats are relatively resistant to hypoxia-induced right ventricular (RV) hypertrophy compared with the Wistar-Kyoto (WKY) strain. These 2 strains were used to examine the genetic basis for the differential response. Methods and Results-Male F 2 offspring from an F344ϫWKY intercross were exposed to hypoxia (10% O 2 ) for 3 weeks, and pulmonary artery pressure and cardiac chamber weights were measured. Genomic DNA was screened by use of polymorphic microsatellite markers across the whole genome (excluding the sex chromosomes). A quantitative trait locus (QTL) for RV weight was identified on rat chromosome 17 (lod score 6.5) that accounted for 22% of the total variance of RV weight in the F 2 population and was independent of pulmonary artery pressure. The peak was centered over marker D17Rat41, close to Chrm3, with a 1-lod support interval of 5 cM. Comparison of homologous regions in mice and humans suggested that Ryr2, the cardiac isoform of the ryanodine receptor, colocalizes with our QTL. A panel of somatic cell hybrids and fluorescence in situ hybridization mapped Ryr2 close to the gene Chrm3 within our QTL.

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The cardiac sarcoplasmic reticulum calcium-release channel: modulation of ryanodine binding and single-channel activity

Cited by 64 publications

References 29 publications

Biochemical characterization, distribution and phylogenetic analysis ofDrosophila melanogasterryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase

Biochemical characterization, distribution and phylogenetic analysis ofDrosophila melanogasterryanodine and IP3 receptors, and thapsigargin-sensitive Ca2+ ATPase

Residue Gln4863 within a Predicted Transmembrane Sequence of the Ca2+ Release Channel (Ryanodine Receptor) Is Critical for Ryanodine Interaction

Right Ventricular Hypertrophy Secondary to Pulmonary Hypertension Is Linked to Rat Chromosome 17

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