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L R Jones

Publications and source records attributed to L R Jones.

At least 55 records · Page 3Linked to original sources
PubMed1999

SERCA1a can functionally substitute for SERCA2a in the heart.

We recently generated a transgenic (TG) mouse model in which the fast-twitch skeletal muscle sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1a) is overexpressed in the heart. Ectopic overexpression of SERCA1a results in remodeling of the cardiac SR containing 80% SERCA1a and 20% endogenous SERCA2a with an approximately 2.5-fold increase in the total amount of SERCA protein (E. Loukianov et al. Circ. Res. 83: 889-897, 1998). We have analyzed the Ca2+ transport properties of membranes from SERCA1a TG hearts in comparison to control hearts. Our data show that the maximal velocity of SR Ca2+ transport was significantly increased ( approximately 1.9-fold) in TG hearts, whereas the apparent affinity of the SERCA pump for Ca2+ was not changed. Addition of phospholamban antibody in the Ca2+ uptake assays increased the apparent affinity for Ca2+ to the same extent in TG and non-TG (NTG) hearts, suggesting that phospholamban regulates the SERCA1a pump in TG hearts. Analysis of SERCA enzymatic properties in TG hearts revealed that the SERCA pump affinity for ATP, the Hill coefficient, the pH dependence of Ca2+ uptake, and the effect of acidic pH on Ca2+ transport were similar to those of NTG hearts. Interestingly, the rate constant of phosphoenzyme decay (turnover rate of SERCA enzyme) was also very similar between TG and NTG hearts. Together these findings suggest that 1) the SERCA1a pump can functionally substitute for SERCA2a and is regulated by endogenous phospholamban in the heart and 2) SERCA1a exhibits several enzymatic properties similar to those of SERCA2a when expressed in a cardiac setting.

Adenosine Triphosphate↗
PubMed1999

Interpretation and design of nonregulatory on-farm feeding trials.

Nonregulatory feeding trials are used to determine the frequency and magnitude of response to a nutritional treatment, the odds of success, and factors that influence the odds and to provide an estimate of potential economic impact. These types of trials are not appropriate for elucidating mechanisms or modes of action. Correct experimental design is critical. Important factors that impact the validity of these trials are animal randomization, potential confounding with time, identification of the proper experimental unit, and adequate replication. Animals should be assigned to treatment without a systematic influence of environmental or physiological factors. The experimental design must account for and remove these influences. The experimental unit is the smallest entity to which the treatment can be applied randomly. In commercial settings, this is often a pen of animals. In a pen feeding situation, the experimental unit is the pen, although measurements may be taken on an individual animal basis. Frequency of data collection generally does not influence the treatment effect; however, it does influence the variance associated with the observations and the power to detect differences in treatments. Statistical methods that account for repeated observations over time are required when analyzing data with multiple observations on the same animal. Improper accounting for environmental changes over time is the most common error. Other errors include improper assignment of animals to treatment, failure to replicate the treatment across multiple experimental units, lack of on-farm oversight, and poor calibration of test equipment.

Animal Feed↗
PubMed1999

Pharmacological characterization of protein phosphatase activities in preparations from failing human hearts.

beta-Adrenoceptor stimulation acts in the heart in part by increasing the phosphorylation state of phospholamban and phospholemman. There is evidence that the beta-adrenoceptor-mediated increase in phospholamban phosphorylation is in part due to inhibition of type 1 phosphatases. The aim of the present study was to elucidate which phosphatases dephosphorylate phospholamban and phospholemman in the human heart. In the past, cardiac serine/threonine phosphatases have been studied using phosphorylase a as substrate. Here, type 1 and type 2A phosphatase activities were studied in preparations from failing human hearts using phosphorylated phospholamban and phospholemman as substrates. Phospholamban and phospholemman phosphatase activity was detectable in human cardiac homogenates. Moreover, using a heparin-Sepharose column, the catalytic subunits of type 1 and type 2A phosphatases could be separated from human ventricles. Okadaic acid and cantharidin inhibited phosphatase activities dephosphorylating phospholamban, phospholemman, and phosphorylase a in homogenates in a concentration-dependent manner. However, okadaic acid was more potent. Cantharidin inhibited type 2A and type 1 activities against all substrates studied with IC50 values <15 nM and >290 nM, respectively. Okadaic acid inhibited type 1 and type 2A phosphatase activities as effectively but 10-30 times more potently than cantharidin. This work provides evidence that in the human heart, type 1 and 2A phosphatases are involved in the dephosphorylation of phospholamban and phospholemman and could play a role in the effects of beta-adrenergic stimulation in the heart.

Animals↗
PubMed1999

Ion currents through mutant phospholemman channel molecules.

Phospholemman (PLM), a small membrane protein with a single transmembrane domain, is a major substrate for protein kinases in muscle. In lipid bilayers, PLM forms ion channels with two unusual features--selectivity for the zwitterion taurine, and switching among cation- and anion-selective conformations. To investigate the molecular determinants of channel behavior, we measured ion currents through (1) PLM channels with point mutations in the extracellular and cytoplasmic domains, (2) chimeric PLM channels with the transmembrane domain of IsK, a K channel subunit, and (3) truncated PLM channels lacking the cytoplasmic domain. Truncated channels and those with a mutation at the cytoplasmic face had altered selectivity. Channels with a point mutation near the extracellular face were non-selective. Switching among channel conformations was less frequent in truncated channels and in channels with point mutations in either the extracellular or cytoplasmic domain. Chimeric channels with a different transmembrane domain had only a small reduction in conductance. We conclude that both the extracellular and cytoplasmic domains play roles in channel selectivity and conformational changes. Cation-binding sites appear to lie in the cytoplasmic domain, and an anion-binding site may reside in the extracellular domain. The cytoplasmic domain may function as a "ball and chain" to regulate channel selectivity.

Amino Acid Sequence↗
PubMed1998

High-level coexpression of the canine cardiac calcium pump and phospholamban in Sf21 insect cells.

Phospholamban is a pentameric transmembrane phosphoprotein that regulates the activity of the Ca(2+)-transporting ATPase (SERCA2a) in cardiac sarcoplasmic reticulum. To better understand the structure and function of phospholamban and its mode of regulation of the ATPase, phospholamban and SERCA2a were coexpressed at high levels in Sf21 insect cells using the baculovirus expression system. SERCA2a was expressed as a functionally active Ca2+ pump, accounting for > or = 20% of the total protein in Sf21 cell microsomes. Wild-type phospholamban, as well as phospholamban with different point mutations in the transmembrane region, inhibited both Ca2+ transport and ATP hydrolysis by the recombinant Ca2+ pump. The inhibition of SERCA2a activity was reversed by an anti-phospholamban monoclonal antibody. The phospholamban molecules studied decreased the apparent Ca2+ affinity of the Ca2+ pump, but had no effect on enzyme velocity measured at saturating Ca2+ concentration. Monomeric phospholamban produced by mutations in the leucine/isoleucine zipper domain decreased the apparent Ca2+ affinity the most, giving stronger inhibition of the Ca2+ pump than even wild-type phospholamban. Thus, the baculovirus cell expression system is ideally suited for examining functional interactions between phospholamban and SERCA2a. The results obtained suggest that the phospholamban monomer may be the active species inhibiting the Ca2+ pump in the cardiac sarcoplasmic reticulum membrane.

Animals↗
PubMed1998

Co-reconstitution and co-crystallization of phospholamban and Ca(2+)-ATPase.

Significant advances have recently been made in understanding the regulation of Ca(2+)-ATPase by phospholamban and in modeling their structures. However, these insights would be furthered by determining the 3-D structure of both proteins within the membrane, thus revealing the structural basis for their interaction. To this end, we have developed methods for reconstituting purified Ca(2+)-ATPase with recombinant phospholamban. After reconstitution at high lipid-to-protein ratios, we have verified their functional association by measuring calcium transport and ATPase activity. Furthermore, we have grown co-crystals after reconstitution at low lipid-to-protein ratios. The structure of Ca(2+)-ATPase has recently been solved by cryoelectron microscopy at 8-A resolution, thus revealing transmembrane alpha-helices. Using a variety of constraints, we have associated these helices with the predicted transmembrane sequences to produce a detailed model for the packing of transmembrane helices. Structure determination of the co-crystals is currently underway, which we hope will eventually reveal the interaction of phospholamban with Ca(2+)-ATPase at a similar level of detail.

Animals↗
PubMed1998

Direct spectroscopic detection of molecular dynamics and interactions of the calcium pump and phospholamban.

In order to test molecular models of cardiac calcium transport regulation, we have used spectroscopy to probe the structures, dynamics, and interactions of the Ca pump (Ca-ATPase) and phospholamban (PLB) in cardiac sarcoplasmic reticulum (SR) and in reconstituted membranes. Electron paramagnetic resonance (EPR) and phosphorescence of probes bound to the Ca pump show that the activity of the pump is quite sensitive to its oligomeric interactions. In cardiac SR, PLB aggregates and inhibits the pump, and both effects are reversed by PLB phosphorylation. Previous analyses of PLB's oligomeric state were only in detergent solutions, so we used EPR and fluorescence to determine the oligomeric structure of PLB in its native state in lipid bilayers. Wild-type PLB is primarily oligomeric in the membrane, while the mutant L37A-PLB is monomeric. For both proteins, phosphorylation shifts the dynamic monomer-oligomer equilibrium toward oligomers, and induces a similar structural change, as indicated by tyrosine fluorescence; yet L37A-PLB is more effective than wild-type PLB in inhibiting and aggregating the pump. Fluorescence energy transfer shows that the Ca pump increases the fraction of monomeric PLB, indicating that the pump preferentially binds monomeric PLB. These results support a reciprocal aggregation model for Ca pump regulation, in which the Ca pump is aggregated and inhibited by association with PLB monomers, and phosphorylation of PLB reverses these effects while decreasing the concentration of PLB monomers. To investigate the structure of the PLB pentamer in more detail, we measured the reactivities of cysteine residues in the transmembrane domain of PLB, and recorded EPR spectra of spin labels attached to these sites. These results support an atomic structural model, based on molecular dynamics simulations and mutagenesis studies, in which the PLB pentamer is stabilized by a leucine-isoleucine zipper within the transmembrane domain.

Animals↗
PubMed1998

Cysteine reactivity and oligomeric structures of phospholamban and its mutants.

To test models for the pentameric structure of phospholamban (PLB) and study its structure and molecular dynamics in SDS solution, we characterized recombinant PLB and several of its mutants by (a) reactivity of cysteine residues toward DTNB [5, 5'-dithiobis(2-nitrobenzoic acid)] and a thiol-reactive spin label, (b) oligomeric state on SDS-PAGE, and (c) EPR of the spin-labeled proteins. WT-PLB has three cysteine residues (36, 41, and 46), all located in the hydrophobic C-terminal transmembrane region. In SDS at pH 7.5, exhaustive reaction with either sulfhydryl reagent resulted in essentially 2 mol of cysteine reacted/mol of WT-PLB, with only slight destabilization of the native pentameric structure. When WT-PLB was denatured in guanidine at pH 8.1, all three cysteines reacted, disrupting the pentamer, which was restored upon cleavage of the disulfide bonds with DTT. In the tetrameric mutant C41L-PLB, the two remaining cysteine residues reacted, reversibly destabilizing the tetramer. In the monomeric mutant L37A-PLB, all three cysteines reacted. The pentameric double cysteine replacement mutant C36,46A-PLB showed negligible reactivity. We conclude that Cys-41 is the unreactive cysteine in PLB and is located at a crucial site for the maintenance of the pentameric structure. EPR spectra in SDS of spin-labeled WT-PLB and mutants correlate with the oligomeric state on SDS-PAGE; oligomeric proteins show decreased spin-label mobility compared with monomers. Molecular dynamics calculations were used to construct an atomic model for the transmembrane region of the PLB pentamer, constrained by previous mutagenesis results and the results of the present study. We conclude that (a) the mobilities of spin-labels attached to PLB and its mutants are sensitive to oligomeric state and (b) the pattern of cysteine reactivity, spin-label mobility, and oligomeric state supports a structural model for the PLB pentamer in which interactions between each pair of subunits are stabilized by a leucine-isoleucine zipper.

Animals↗
PubMed1998

Phosphorylation-induced structural change in phospholamban and its mutants, detected by intrinsic fluorescence.

We have used intrinsic fluorescence to test the hypothesis that phosphorylation induces a conformational change in phospholamban (PLB), a regulatory protein in cardiac sarcoplasmic reticulum (SR). Phosphorylation of PLB, which relieves inhibition of the cardiac Ca-ATPase, has been shown to decrease the mobility of PLB in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In the present study, we found that this mobility shift depends on the acrylamide concentration in the gel, suggesting that phosphorylation increases the effective Stokes radius. To further characterize this structural change, we performed spectroscopic experiments under the conditions of SDS-PAGE. CD indicated that phosphorylation at Ser-16 does not change PLB's secondary structure significantly. However, the fluorescence of Tyr-6 in the cytoplasmic domain of PLB changed significantly upon PLB phosphorylation: phosphorylation increased the fluorescence quantum yield and decreased the quenching efficiency by acrylamide, suggesting a local structural change that decreases the solvent accessibility of Tyr-6. A point mutation (L37A) in the transmembrane domain, which disrupts PLB pentamers and produces monomers in SDS-PAGE and in lipid bilayers, showed similar phosphorylation effects on fluorescence, indicating that subunit interactions within PLB are not crucial for the observed conformational change in SDS. When PLB was reconstituted into dioleoylphosphatidylcholine (DOPC) lipid bilayers, similar phosphorylation effects in fluorescence were observed, suggesting that PLB behaves similarly in response to phosphorylation in both detergent and lipid environments. We conclude that phosphorylation induces a structural change within the PLB protomer that decreases the solvent accessibility of Tyr-6. The similarity of this structural change in monomers and pentamers is consistent with models in which the PLB monomer is sufficient for the phosphorylation-dependent regulation of the Ca-ATPase.

Acrylamide↗
PubMed1998

Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing calsequestrin.

To probe the physiological role of calsequestrin in excitation-contraction coupling, transgenic mice overexpressing cardiac calsequestrin were developed. Transgenic mice exhibited 10-fold higher levels of calsequestrin in myocardium and survived into adulthood, but had severe cardiac hypertrophy, with a twofold increase in heart mass and cell size. In whole cell-clamped transgenic myocytes, Ca2+ channel- gated Ca2+ release from the sarcoplasmic reticulum was strongly suppressed, the frequency of occurrence of spontaneous or Ca2+ current-triggered "Ca2+ sparks" was reduced, and the spark perimeter was less defined. In sharp contrast, caffeine-induced Ca2+ transients and the resultant Na+-Ca2+ exchanger currents were increased 10-fold in transgenic myocytes, directly implicating calsequestrin as the source of the contractile-dependent pool of Ca2+. Interestingly, the proteins involved in the Ca2+-release cascade (ryanodine receptor, junctin, and triadin) were downregulated, whereas Ca2+-uptake proteins (Ca2+-ATPase and phospholamban) were unchanged or slightly increased. The parallel increase in the pool of releasable Ca2+ with overexpression of calsequestrin and subsequent impairment of physiological Ca2+ release mechanism show for the first time that calsequestrin is both a storage and a regulatory protein in the cardiac muscle Ca2+-signaling cascade. Cardiac hypertrophy in these mice may provide a novel model to investigate the molecular determinants of heart failure.

Animals↗
PubMed1998

Differential effects of general anesthetics on the quaternary structure of the Ca-ATPases of cardiac and skeletal sarcoplasmic reticulum.

The effects of the general anesthetics hexanol, halothane, and diethyl ether on Ca-ATPase activity and on the oligomeric state of the Ca-ATPase of sarcoplasmic reticulum (SR) from cardiac and skeletal muscle were investigated. The effects of these general anesthetics on Ca-ATPase activity were similar in cardiac and skeletal SR and were characterized by stimulation of Ca-ATPase activity at lower concentrations of anesthetics and inhibition at higher concentrations. The distribution of the Ca-ATPase among its oligomeric states was estimated from the time-resolved phosphorescence anisotropy (TPA) decay of SR in which Ca-ATPase was covalently labeled with erythrosin isothiocyanate (ERITC) or with erythrosin iodoacetamide (ERIA). In contrast to the similar responses of Ca-ATPase activity, there were marked differences in the responses to general anesthetics of the TPA decay between cardiac and skeletal SR. In cardiac SR hexanol, halothane, and diethyl ether caused pronounced increases in the limiting anisotropy at very long times (r infinity), which indicate increases in the fraction of oligomers too large to rotate on the millisecond time scale of the experiments. In skeletal SR, by contrast, there were no significant changes in r infinity in response to the three general anesthetics. This difference between cardiac and skeletal SR in response to general anesthetics is not due to the presence of phospholamban in cardiac SR, since SR from AT-1 cells, which have the SERCA2a isoform of Ca-ATPase, but only trace levels of phospholamban, have increases in r infinity in response to the general anesthetics that resemble those in cardiac SR. Experiments with cardiac SR labeled with ERIA give similar results, showing that the results with ERITC are not an artifact of the labeling procedure. Increasing the ionic strength with LiCl diminished the proportion of large immobile oligomers of cardiac Ca-ATPase under control conditions but enhanced the formation of large oligomers in response to hexanol.

Anesthetics, General↗
PubMed1998

Structural domains in phospholemman: a possible role for the carboxyl terminus in channel inactivation.

Phospholemman (PLM) is a small (72-amino acid) transmembrane protein found in cardiac sarcolemma that is a major substrate for several protein kinases in vivo. Detailed structural data for PLM is lacking, but several studies have described an ion conductance that results from PLM expression in oocytes. Moreover, addition of purified PLM to lipid bilayers generates similar ion currents, suggesting that the PLM molecule itself might be sufficient for channel formation. To provide a framework for understanding the function of PLM, we investigated PLM topology and structure in sarcolemmal membrane vesicles and analyzed purified recombinant PLM. Immunoblot analyses with site-specific antibodies revealed that the extracellular segment (residues 1 to 17) exists in a protected configuration highly resistant to proteases, even in detergent solutions. The intracellular portion of the molecule (residues 38 to 72), in contrast, was highly susceptible to proteases. Trypsin treatment produced a limit peptide (residues 1 to 43), which showed little change in electrophoretic mobility in SDS gels and retained the ion-channel activity in lipid bilayers that is characteristic of the full-length protein. In addition, we found that conductance through PLM channels exhibited rapid inactivation during depolarizing ramps at voltages greater than +/- 50 mV, Channels formed by trypsinized PLM or recombinant PLM 1-43 exhibited dramatic reductions in voltage-dependent inactivations. Our data point to distinct domains within the PLM molecule that may correlate with functional properties of channel activity observed in oocytes and lipid bilayers.

Amino Acid Sequence↗
PubMed1998

Targeted overexpression of phospholamban to mouse atrium depresses Ca2+ transport and contractility.

Phospholamban is a small phosphoprotein regulator of the Ca2+-pump of cardiac sarcoplasmic reticulum. Dephosphorylated phospholamban inhibits the Ca2+-pump and depresses contractility, whereas phosphorylation of phospholamban by cAMP-activated mechanisms relieves this inhibition and increases contractility. In order to better understand the function of phospholamban in living systems, a transgenic mouse model was established employing targeted overexpression of phospholamban to the atrium, which normally expresses low levels of the protein. Overexpression was achieved by fusing the alpha-MHC-promoter or the ANF-promoter to the phospholamban gene. Double transgenic mice were created by mating mice positive for each transgene. In single transgenic lineages, phospholamban was overexpressed four to six-fold in left atrium. In the double transgenic mice, phospholamban was overexpressed eight- to nine-fold. In the three transgenic strains. Ca2+ uptake by the sarcoplasmic reticulum was depressed to 22-30% of control values at low ionized calcium. This depression of Ca2+ uptake was largely reversed by addition of a phospholamban monoclonal antibody. In the atrial muscle strips, the time course of contraction was increased in a concentration-dependent manner by overexpression of phospholamban, whereas the basal developed tension was decreased up to 85% by phospholamban-overexpression. In all transgenic lineages, isoproterenol, a beta-adrenoceptor agonist, reversed the depression of contractility caused by overexpression of phospholamban and significantly shortened time parameters to levels approaching control values. These data demonstrate that overexpression of phospholamban in a mammalian myocardial tissue normally deficient in the protein substantially inhibits basal contractility, and furthermore suggest that in myocardial tissues containing high levels of the protein, phosphorylation of phospholamban can account for many of the positive inotropic and lusitropic effects of beta-adrenergic stimulation.

Animals↗
PubMed1998

Phospholamban: protein structure, mechanism of action, and role in cardiac function.

A comprehensive discussion is presented of advances in understanding the structure and function of phospholamban (PLB), the principal regulator of the Ca2+-ATPase of cardiac sarcoplasmic reticulum. Extensive historical studies are reviewed to provide perspective on recent developments. Phospholamban gene structure, expression, and regulation are presented in addition to in vitro and in vivo studies of PLB protein structure and activity. Applications of breakthrough experimental technologies in identifying PLB structure-function relationships and in defining its interaction with the Ca2+-ATPase are also highlighted. The current leading viewpoint of PLB's mechanism of action emerges from a critical examination of alternative hypotheses and the most recent experimental evidence. The potential physiological relevance of PLB function in human heart failure is also covered. The interest in PLB across diverse biochemical disciplines portends its continued intense scrutiny and its potential exploitation as a therapeutic target.

Animals↗
PubMed1998

Long-term beta adrenoceptor-mediated alteration in contractility and expression of phospholamban and sarcoplasmic reticulum Ca(++)-ATPase in mammalian ventricle.

We studied the influence of prolonged administration of the beta adrenoceptor agonist isoproterenol on contractile parameters and expression of sarcoplasmic reticulum (SR) Ca(++)-ATPase and phospholamban, genes important for Ca++ uptake into the SR. Isoproterenol (Iso), 0.9% NaCl (Ctr), propranolol (Prop) or Iso plus Prop were administered to rats by subcutaneous infusion with osmotic minipumps for 1, 2, 3, 4, 8, 13 and 26 days, respectively. The positive inotropic effect of Iso was impaired in rats pretreated with Iso in vivo. Iso pretreatment shortened time to peak tension (TPT) by 28%, time of relaxation (RT) by 27% and total contraction time (TCT) by 27% compared with the appropriate controls (day 2). The shortening of time-dependent contractile indices started after 1 day of Iso pretreatment, reached a maximum after 2 days and remained reduced for 4 days. Longer treatment by Iso failed to affect time parameters, whereas the positive inotropic effect of Iso added to the isolated muscles persisted. The shortened contractile time parameters were accompanied by diminished mRNA and protein expression of phospholamban (PLB) and SR-Ca(++)-ATPase (SERCA). The mRNA levels for PLB and SERCA were maximally reduced by 31 +/- 1.3% and 41 +/- 1.4% in the Isopretreated group (2 days) respectively. The reduced mRNA levels were accompanied by reduced levels of the corresponding proteins. It is concluded that altered levels of PLB and SERCA probably account for the noted changes in contractile time parameters in the mammalian heart.

Animals↗
PubMed1997

Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane.

Several key proteins have been localized to junctional sarcoplasmic reticulum which are important for Ca2+ release. These include the ryanodine receptor, triadin, and calsequestrin, which may associate into a stable complex at the junctional membrane. We recently purified and cloned a fourth component of this complex, junctin, which exhibits homology with triadin and is the major 125I-calsequestrin-binding protein detected in cardiac sarcoplasmic reticulum vesicles (Jones, L. R., Zhang, L., Sanborn, K., Jorgensen, A. O., and Kelley, J. (1995) J. Biol. Chem. 270, 30787-30796). In the present study, we have examined the binding interactions between the cardiac forms of these four proteins with emphasis placed on the role of junctin. By a combination of approaches including calsequestrin-affinity chromatography, filter overlay, immunoprecipitation assays, and fusion protein binding analyses, we find that junctin binds directly to calsequestrin, triadin, and the ryanodine receptor. This binding interaction is localized to the lumenal domain of junctin, which is highly enriched in charged amino acids organized into "KEKE" motifs. KEKE repeats are also found in the common lumenal domain of triadin, which likewise is capable of binding to calsequestrin and the ryanodine receptor (Guo, W., and Campbell, K. P. (1995) J. Biol. Chem. 270, 9027-9030). It appears that junctin and triadin interact directly in the junctional sarcoplasmic reticulum membrane and stabilize a complex that anchors calsequestrin to the ryanodine receptor. Taken together, these results suggest that junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release.

Animals↗