Biology subjects

Sakurai, T.

Publications and source records attributed to Sakurai, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Multimodal phenotyping reveals plant-food-related dietary information in serum Raman spectra of community-dwelling Japanese adults

Healthy dietary patterns are associated with long-term health, but diet-quality scores do not reveal how habitual dietary information is represented in human biological phenotypes. Here we linked habitual dietary assessment with preceding health records and contemporaneous clinical chemistry, serum metabolomics and serum Raman spectra in community-dwelling Japanese adults. Higher diet quality corresponded to a more favorable preceding health profile, but did not define discrete states across contemporary multivariate phenotypes. Instead, specific dietary information was recoverable across these layers: Raman spectra provided predictive information complementary to clinical and metabolomic measurements for multiple dietary variables. Raman variation corresponding to {beta}-carotene equivalent could be traced to carotenoid-assigned bands and aligned with a broader plant-food-related dietary dimension. These findings show that habitual diet is represented not as a single biological state but through biologically traceable dietary dimensions distributed across complementary phenotypic layers.

bioinformatics↗

bioRxiv2026

A thermoregulatory design principle for transitions into hypometabolism

Mammals entering torpor or hibernation undergo an abrupt transition from normothermia to hypothermia, yet how thermoregulation enables this switch remains poorly understood. Here, we identify dynamical signatures that precede these transitions and a mathematical principle that can generate them. In fasting-induced torpor in mice, body-temperature fluctuations increased before torpor onset, providing an early-warning signal that tracked proximity to the transition better than temperature decline alone. A heat-balance model showed that reducing how strongly the effective heat-loss coefficient depends on body temperature reorganizes thermoregulatory stability, allowing a low-temperature equilibrium to emerge while the normothermic state remains stable. This organization is consistent with a symmetry-broken pitchfork involving a saddle-node. Similar increases in temperature fluctuations preceded hibernation onset in hamsters. These findings link pre-transition temperature dynamics to changes in the underlying thermoregulatory landscape and provide a framework for detecting and understanding transitions from normothermia to hypothermia.

systems biology↗

bioRxiv2026

Hypothermic Conditions Impair GnRH Pulse Generator Activity and Gametogenesis

Mammalian reproductive function is driven by arcuate kisspeptin neurons, pacemakers of gonadotropin secretion. During energy shortages, animals reallocate resources from reproduction to survival; however, the underlying neural mechanisms remain elusive. Here we used fiber photometry to chronically monitor synchronized episodes of arcuate kisspeptin neuron activity (SEskiss) in adult mice under various energy-saving conditions. In both sexes, SEskiss frequency was markedly suppressed during fasting-induced torpor and pharmacologically induced hypothermia, whereas hypometabolism alone had no discernible effect. A Q neuron-induced hypothermic state (QIH) robustly suppressed SEskiss, leading to impaired gamete maturation, whereas warming the body temperature during QIH fully restored SEskiss frequency. These findings demonstrate that hypothermia, rather than hypometabolism, is the primary driver of suppression of the hypothalamic reproductive axis during energy-saving conditions. This study provides insights into how thermal signals act as critical gatekeepers in the mammalian reproductive system.

neuroscience↗

bioRxiv2026

Systematic benchmarking of zero-shot utility and robustness in single-cell transcriptomic foundation models

Single-cell foundation models (scFMs) have emerged as powerful representation learning approaches for single-cell transcriptomics. However, the utility and robustness of their pretrained representations across diverse analytical tasks and data conditions remain insufficiently characterized, particularly in zero-shot settings without task-specific fine-tuning. Here, we systematically analyze zero-shot performance of single-cell transcriptomic representations across 20 methods, 6 downstream tasks and 1,607 datasets comprising nearly 21.8 million cells. We evaluate model behavior along three complementary dimensions: utility on original datasets, robustness to controlled changes in dataset structure, and exploratory associations between dataset characteristics and performance variation. Our results show that scFM performance is strongly task dependent, with no single method consistently outperforming others across cell- and gene-level analyses. Notably, high utility on original datasets did not necessarily translate into robustness under structural perturbations, and several top-ranking methods were sensitive to changes in cell number, gene number, class composition, class imbalance, and batch complexity. Conventional statistical and task-specific methods remained competitive in several settings, while greater computational cost did not consistently correspond to better performance. Driver analyses further identified task-specific associations between performance and dataset characteristics, including cell-type complexity, train-test class overlap, batch number, and regulatory target-set size. Together, these findings show that the zero-shot utility and robustness of pretrained scFM representations depend jointly on analytical task and dataset structure. Our study provides a practical basis for context-aware representation selection and underscores the importance of evaluating structural robustness alongside utility when developing and applying scFMs.

bioinformatics↗

bioRxiv2026

Structural basis for Ca2+-dependent, RyR2-selective stabilization by Ryanozole in CPVT

The cardiac ryanodine receptor (RyR2) is a Ca{superscript 2} release channel essential for excitation-contraction coupling. RyR2 mutations cause severe arrhythmogenic disorders, including catecholaminergic polymorphic ventricular tachycardia (CPVT), through gain-of-function (GOF) effects leading to aberrant Ca{superscript 2} release. We have recently developed Ryanozole, a potential therapeutic compound for CPVT, which selectively stabilizes RyR2 in a Ca2+-dependent manner. Here, we define the mechanism of action of Ryanozole by combining high-resolution cryo-electron microscopy, targeted mutagenesis and functional assays. Ryanozole binds to the interface between the Ca{superscript 2}-binding site and the pore-forming S6 helix, interfering with conformational changes required for Ca{superscript 2}-induced channel opening at low Ca2+. We identified key residues for the binding and isoform-specific modulation of Ryanozole. Notably, Ryanozole-bound RyR2 retains its ability to open at high Ca2+ via unique conformational changes. These findings provide a structural basis for CPVT-targeted therapy and redefine the paradigm of small molecule-based regulation of large ion channels.

biochemistry↗

bioRxiv2026

Psilocybin reshapes cortical inhibition through selective interneuron recruitment

Psychedelics show therapeutic potential for treating psychiatric disorders. While studies have emphasized the roles of cortical pyramidal cells, GABAergic neurons also express serotonin receptors and are therefore likely targets of psychedelics. In this study, we determine the effect of psilocybin on the activity dynamics of major GABAergic cell types in the mouse medial frontal cortex. Psilocybin reduces the firing of somatostatin-expressing interneurons, but increases the activity of parvalbumin-expressing interneurons. This cell type-specific response is unlikely to involve vasoactive intestinal peptide-expressing interneurons. Instead, pharmacological blockade and conditional knockout experiments demonstrate that psilocybin acts on the 5-HT1A receptor at SST interneurons, which contributes to the drugs long-term behavioral effects. Collectively, the results reveal that the classic psychedelic psilocybin alters cortical inhibition in a cell type-specific manner.

neuroscience↗

bioRxiv2025

Repetitive Hibernation-Like State Suppresses the Progression of Amyloid Pathology

Alzheimers disease (AD) is characterized by the gradual accumulation of amyloid pathology before the onset of cognitive impairment, yet effective strategies to alter disease progression remain limited. Here, we tested whether induction of a hibernation-like physiological state can slow amyloid pathology in an AD mouse model. To achieve sustained effects, we developed a protocol for repeated induction of a hypometabolic/hypothermic state and found that it significantly slowed plaque accumulation in a duration-dependent manner. This intervention also attenuated neuroinflammation and the formation of dystrophic neurites associated with plaques. Notably, this approach does not target specific molecular pathways but instead modulates global brain state. Our findings establish a proof-of-concept for a brain-state- based therapeutic paradigm for modifying disease progression in AD.

neuroscience↗

bioRxiv2025

Artificial hibernation uncovers distinct synaptic engram architecture for memory retention

The memory trace at the neuronal and synaptic levels remains controversial. Stable, larger spines are thought to support memory, but the high turnover of dendritic spines and the drifting of neuronal representations following memory formation suggest alternative possibilities. To elucidate a structural trace underlying memory retention, we utilize a mouse model of artificial hibernation. During hibernation, hippocampal neurons exhibited a substantial reduction in their activity and an extensive elimination of dendritic spines and synapses. Despite these changes, their memory and associated hippocampal neuronal representations are intact after arousal. We find that a subset of spines is maintained during hibernation. These spatially clustered engram-engram synapses are exclusively protected from elimination and characterized by synaptic contacts with multi-synaptic boutons. These findings suggest that synaptic engram architecture, rather than larger spines per se, is resilient to network remodeling and underlies long-term memory retention.

neuroscience↗

bioRxiv2025

Dissecting Medullary Raphe Neurons Regulating Multiple Thermogenic Pathways

Thermogenesis is critical for survival and health in mammals. Although the thermoregulatory systems in the preoptic area are well documented, the downstream processing of these central signals--particularly by medullary neurons involved in the control of shivering and sympathetic activation of brown adipose tissue (BAT)--remains incompletely understood. Here we show that vesicular glutamate transporter type 3 (vGluT3)-expressing neurons in the medullary raphe pallidus (RPa) become active immediately before a spontaneous increase in body temperature. These neurons remain inactive under experimentally induced hypometabolic conditions and are necessary for rapid recovery from hypothermia. Furthermore, they communicate with multiple brainstem systems involved in the integration of thermal cues. Notably, RPa-vGluT3 neurons can drive shivering via specific brainstem premotor neurons, in addition to regulating sympathetic outflows for BAT thermogenesis and heat-conserving piloerection. These data indicate that RPa-vGluT3 neurons function as medullary hubs, coordinating sympathetic and somatic motor outputs to increase body temperature. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/673572v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@12d2e79org.highwire.dtl.DTLVardef@1463498org.highwire.dtl.DTLVardef@27058eorg.highwire.dtl.DTLVardef@1ddee56_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIRaphe pallidus-vGluT3 neurons are active immediately preceding a spontaneous rise in body temperature. C_LIO_LIThey are suppressed during the state of Q-neuron-induced hypothermia and hypometabolism (QIH). C_LIO_LIThey connect with multiple brainstem pathways involved in thermoregulation. C_LIO_LIThey control shivering via brainstem somatic premotor neurons. C_LI

neuroscience↗

bioRxiv2025

Artificially induced torpor during pregnancy impairs fetal growth in mice

Fetal development in endothermic mammals relies on a tightly regulated maternal body temperature. In animal models, deviations from normothermia during gestation cause fetal developmental abnormalities. However, the direct and physiological manipulation of the maternal core temperature has been technologically challenging, as traditional methods involve the imposition of external thermal stress. Recent advances in the identification of thermoregulatory neurons in the mouse preoptic area have allowed precise control of maternal body temperature without altering environmental conditions. Here we show that the activation of excitatory neurons in the medial preoptic area (MPO) induces a torpor-like hypothermic state in pregnant mice. When induced during early gestation, this state resulted in pregnancy loss, likely due to implantation failure. Hypothermia in mid- and late-gestation reduced fetal liver and kidney size and caused severe growth retardation. Similar outcomes were observed following pyroglutamylated RFamide peptide (Qrfp)-expressing neuron activation in the MPO, whereas inhibitory neuron activation had minimal effect. Furthermore, activating MPO excitatory neurons projecting to the dorsomedial hypothalamic nucleus reproduced both the torpor-like state and fetal growth retardation. These results underscore the importance of a stable maternal body temperature in fetal development and establish a new model for studying the effects of altered maternal temperature on embryogenesis.

neuroscience↗

bioRxiv2024

A novel RyR2-selective stabilizer prevents and ameliorates severe arrhythmias in stress-induced ventricular tachycardia

Background and PurposeAberrant activation of the type 2 ryanodine receptor (RyR2) causes lethal arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). Developing drugs that suppress RyR2 hyperactivation may be key to novel arrhythmia treatments. This study evaluated the antiarrhythmic potential of Ryanozole, a recently developed novel RyR2 modulator with high affinity and selectivity, using CPVT mouse models harboring mutant RyR2s. Experimental approachIn vitro effects of Ryanozole were evaluated by ER Ca2+-based assay and [3H]Ryanodine binding assay using RyR2-expressing HEK293 cells. Two lines of mice with different arrhythmia severity, RyR2-R420W and -K4750Q, were employed for in vivo assessments. Intracellular Ca2+ signals were analyzed in isolated cardiomyocytes using Cal520. Antiarrhythmic effects were evaluated by ECG under catecholaminergic challenge in anesthetized mice and during spontaneous arrhythmias in conscious mice. ECG and echocardiographic parameters were evaluated before and after drug administration. Key resultsRyanozole inhibited both wild type and mutant RyR2s with similar IC50 of 15-40 nM. The inhibition was more potent at lower cytosolic Ca2+ concentrations. It suppressed Ca2+ waves and Ca2+ sparks without affecting action potential-evoked Ca2+ transients. Ryanozole effectively prevented adrenaline-induced arrhythmias and rapidly terminated spontaneous arrhythmias during daily activity. Importantly, Ryanozole did not impair cardiac conduction or contractility, unlike conventional antiarrhythmic drugs. Conclusions and implicationsRyanozole strongly suppresses RyR2 under diastolic Ca2+ conditions, thereby preventing the arrhythmogenic trigger of aberrant Ca2+ release. This mechanism likely provides potent antiarrhythmic effects while preserving cardiac function. Ryanozole is a promising therapeutic candidate treating RyR2-mediated arrhythmias, such as CPVT.

pharmacology and toxicology↗

bioRxiv2024

T-scope V4: miniaturized microscope for optogenetic tagging in freely behaving animals

A miniaturized microscope (i.e., miniscope) enables the imaging of neuronal activity using calcium sensors while simultaneously manipulating that activity using opsins in freely moving animals. However, many miniscopes use light-emitting diodes with broadband emission, leading to unintentional opsin stimulation by light intended solely for calcium sensor activation (a phenomenon referred to as "biological crosstalk"). To address this issue, we previously developed a miniscope including a port for chosen light sources, such as lasers, by restructuring the open-source UCLA Miniscope v3. However, targeting the same neuronal soma for both excitable opsin stimulation and calcium sensor imaging remained a challenge. Here, we integrated features from the UCLA Miniscope v4 into our new T-scope V4 miniscope. In optogenetic tagging experiments, we demonstrated that a 445-nm blue laser can be used to image neuronal activity with the calcium sensor GCaMP6s without inadvertently stimulating the ChrimsonR opsin, allowing for simultaneous neuronal activity imaging and manipulation in freely moving mice. Thus, the T-scope V4 can serve as a powerful tool for probing causal relationships between neuronal activity and its function in living animals. HighlightsO_LIWe developed the T-scope V4 that integrates features of the UCLA Miniscope v4 C_LIO_LIThis miniscope prevents "biological crosstalk" between sensors and opsins C_LIO_LIThis tool can help probe causal brain-behavior relationships in living animals C_LI

neuroscience↗

bioRxiv2024

Three years of insecticide resistance evolution and associated mechanisms in Aedes aegypti populations of Ouagadougou, Burkina Faso.

BackgroundResistance to insecticides is spreading among populations of Aedes aegypti, the primary vector of important human arboviruses. The escalating insecticide resistance poses a significant threat to dengue vector control, with an expanding number of countries affected by the disease. To gain a deeper insight into the evolution of insecticide resistance, it is essential to have longitudinal surveillance results, which are currently lacking, particularly from African Ae. aegypti populations. Here we report on three-years of surveillance of Ae. aegypti susceptibility to insecticide resistance phenotypes and associated kdr mutations in Burkina Faso, a country with regular dengue outbreaks. MethodsAe. aegypti susceptibility to insecticides and the V410L, V1016I, and F1534C kdr target site mutations linked to pyrethroid insecticide resistance were monitored in Ouagadougou from 2016 to 2018. Larvae were collected from artificial containers at two sites and reared to adulthood in an insectary. Bioassays were conducted on female adults, alongside with a laboratory-susceptible strain, following standard WHO protocols. Allele-specific PCR genotyping assays were utilized to identify the V410L, V1016I, and F1534C kdr pyrethroid target site mutations. ResultsBioassays revealed a high level of resistance to permethrin and deltamethrin that progressively increased over the three-year period in both localities. The 1534C mutation was nearly fixed throughout the three years at each locality, and while the closely related 410L and 1016I mutations did not vary between localities, their frequency notably increased from 2016 to 2018. Interestingly, Ae. aegypti populations in both areas remained susceptible to bendiocarb, fenitrothion, and malathion. Modeling the mortality data further confirmed the escalating resistance trend over the years and emphasized the significant role played by the three kdr mutations in conferring resistance to pyrethroids. ConclusionMortality rates indicate that Ae. aegypti populations from Ouagadougou are becoming increasingly resistant to pyrethroid insecticides, likely due to an increase in the frequencies of the 410L and 1016I kdr mutations. Organophosphate insecticides are likely to be better alternative options for control.

evolutionary biology↗

bioRxiv2024

DenoiseST: A dual-channel unsupervised deep learning-based denoising method to identify spatial domains and functionally variable genes in spatial transcriptomics

Spatial transcriptomics provides a unique opportunity for understanding cellular organization and function in a spatial context. However, spatial transcriptome exists the problem of dropout noise, exposing a major challenge for accurate downstream data analysis. Here, we proposed DenoiseST, a dual-channel unsupervised adaptive deep learning-based denoising method for data imputing, clustering, and identifying functionally variable genes in spatial transcriptomics. To leverage spatial information and gene expression profiles, we proposed a dual-channel joint learning strategy with graph convolutional networks to sufficiently explore both linear and nonlinear representation embeddings in an unsupervised manner, enhancing the discriminative information learning ability from the global perspectives of data distributions. In particular, DenoiseST enables the adaptively fitting of different gene distributions to the clustered domains and employs tissue-level spatial information to accurately identify functionally variable genes with different spatial resolutions, revealing their enrichment in corresponding gene pathways. Extensive validations on a total of 18 real spatial transcriptome datasets show that DenoiseST obtains excellent performance and results on brain tissue datasets indicate it outperforms the state-of-the-art methods when handling artificial dropout noise with a remarkable margin of [~]15%, demonstrating its effectiveness and robustness. Case study results demonstrate that when applied to identify biological structural regions on human breast cancer spatial transcriptomic datasets, DenoiseST successfully detected biologically significant immune-related structural regions, which are subsequently validated through Gene Ontology (GO), cell-cell communication, and survival analysis. In conclusion, we expect that DenoiseST is a novel and efficient method for spatial transcriptome analysis, offering unique insights into spatial organization and function.

bioinformatics↗

bioRxiv2023

Sequential Transitions of Male Sexual Behaviours Driven by Dual Acetylcholine-Dopamine Dynamics

The neural mechanisms regulating sequential transitions of male sexual behaviors, such as mounting, intromission, and ejaculation, in the brain remain unclear. Here, we report that dopamine (DA) and acetylcholine (ACh) dynamics in the ventral shell of the nucleus accumbens (vsNAc) closely aligns with serial transitions of sexual behaviors in male mice. During intromission, the vsNAc exhibits dual ACh-DA rhythms generated by reciprocal regulation between ACh and DA signaling via nicotinic acetylcholine (nAChR) and dopamine D2 (D2R) receptors. Knockdown of choline acetyl transferase (ChAT) or D2R in the vsNAc diminished the likelihood of intromission and ejaculation. Optogenetic manipulations reveal that DA signaling sustains male sexual behaviors by suppressing activities of D2RvsNAc neurons. Moreover, ACh signaling promotes the initiation of mounting and intromission, but also induces the intromission-to-ejaculation transition by triggering a slowdown of DA rhythm. Therefore, dual ACh-DA dynamics harmonize in the vsNAc to drive sequential transitions of male mating behaviors.

neuroscience↗

bioRxiv2023

Synaptic plasticity in the medial preoptic area of male mice encodes social experiences with female and regulates behavior toward young

A dramatic shift from aggressive infanticidal to paternal behaviors is an essential event for male mice after mating. While the central part of the medial preoptic area (cMPOA) has been shown to critically mediate the paternal behaviors in mice, how this brain region becomes activated by mating and subsequent interaction with pups has not been investigated. Here, we demonstrate that the reduction in inhibitory synaptic strength towards the cMPOA provided by posterior-dorsal medial amygdala (MePD) neurons is a key event for the post-mating behavioral shift in males. Consistent with this, we found optogenetic disinhibition of MeCartpt to the cMPOA synapses reduces male aggression towards pups. The cMPOA of paternal mice mediated pup-induced neural plastic changes in the bed nucleus of the stria terminalis. These findings provide possible functions of cMPOA neural circuits required for the reception to young in male mice.

zoology↗

bioRxiv2023

Carvedilol suppresses ryanodine receptor-dependent Ca2+ bursts in human neurons bearing PSEN1 variants found in early onset Alzheimer's disease

Seizures are increasingly being recognized as the hallmark of Alzheimers disease (AD). Neuronal hyperactivity can be a consequence of neuronal damage caused by abnormal amyloid {beta} (A{beta}) depositions. However, it can also be a cell-autonomous phenomenon causing AD by A{beta}-independent mechanisms. Indeed, various studies using animal models showed that Ca2+ releases from the endoplasmic reticulum (ER) via type 1 inositol triphosphate receptors (InsP3R1s) and ryanodine receptors (RyRs). To investigate which is the main pathophysiological mechanism in human neurons, we measured Ca2+ signaling in neural cells derived from three early-onset AD patients harboring variants of Presenilin-1 (PSEN1 p.A246E, p.L286V, and p.M146L). Of these, it has been reported that PSEN1 p.A246E and p.L286V did not produce a significant amount of abnormal A{beta}. We found that all PSEN1-mutant neurons, but not wild-type, caused abnormal Ca2+-bursts in a manner dependent on the calcium channel, Ryanodine Receptor 2 (RyR2). Indeed, carvedilol, anRyR2 inhibitor, and VK-II-86, an analog of carvedilol without the {beta}-blocking effects, sufficiently eliminated the abnormal Ca2+ bursts. In contrast, Dantrolene, a RyR1 inhibitor, and Xestospongin c, an IP3R inhibitor, did not attenuate the Ca2+-bursts. The RNA-Seq data revealed that ER-stress responsive genes were increased, and mitochondrial Ca2+-transporter genes were decreased in PSEN1A246E cells compared to the WT neurons. Thus, we propose that aberrant Ca2+ signaling is a key link between human pathogenic PSEN1 variants and cell-intrinsic hyperactivity prior to deposition of abnormal A{beta}, offering prospects for the development of targeted prevention strategies for at-risk individuals. One Sentence SummaryAberrant Ca2+-signaling causes PSEN1-related early onset Alzheimers disease.

neuroscience↗

bioRxiv2023

Screening for novel RyR2 inhibitors by ER Ca2+ monitoring

Type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic/sarcoplasmic reticulum (ER/SR) that plays a central role in the excitation-contraction coupling in the heart. Hyperactivity of RyR2 has been linked to ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and heart failure, where spontaneous Ca2+ release via hyperactivated RyR2 depolarizes diastolic membrane potential to induce triggered activity. In such cases, drugs that suppress RyR2 activity are expected to prevent the arrhythmias, but there is no clinically available RyR2 inhibitors at present. In this study, we searched for RyR2 inhibitors from a well-characterized compound library using a recently developed ER Ca2+-based assay, where the inhibition of RyR2 activity was detected by the increase in ER Ca2+ signals from R-CEPIA1er, a genetically encoded ER Ca2+ indicator, in RyR2-expressing HEK293 cells. By screening 1535 compounds in the library, we identified three compounds (chloroxylenol, methyl orsellinate and riluzole) that greatly increased the ER Ca2+ signal. All of the three compounds suppressed spontaneous Ca2+ oscillations in RyR2-expressing HEK293 cells and correspondingly reduced the Ca2+-dependent [3H]ryanodine binding activity. In cardiomyocytes from RyR2-mutant mice, the three compounds effectively suppressed abnormal Ca2+ waves without substantial effects on the action-potential-induced Ca2+ transients. These results confirm that ER Ca2+-based screening is useful for identifying modulators of ER Ca2+ release channels and suggest that RyR2 inhibitors have potential to be developed as a new category of antiarrhythmic drugs. Significance statementWe successfully identified three compounds having RyR2 inhibitory action from a well-characterized compound library using an ER Ca2+-based assay, and demonstrated that these compounds suppressed arrhythmogenic Ca2+ wave generation without substantially affecting physiological action-potential induced Ca2+ transients in cardiomyocytes. This study will facilitate the development of RyR2 specific inhibitors as a potential new class of drugs for life-threatening arrhythmias induced by hyperactivation of RyR2.

pharmacology and toxicology↗