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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 415 records · Page 23
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Gene Regions Responding to Skeletal Muscle Atrophy

Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

Booth, Frank W.↗
DOE OSTI2020

Xylella fastidiosa causes transcriptional shifts that precede tylose formation and starch depletion in xylem

Abstract Pierce's disease (PD) in grapevine ( Vitis vinifera ) is caused by the bacterial pathogen Xylella fastidiosa . X. fastidiosa is limited to the xylem tissue and following infection induces extensive plant‐derived xylem blockages, primarily in the form of tyloses. Tylose‐mediated vessel occlusions are a hallmark of PD, particularly in susceptible V. vinifera . We temporally monitored tylose development over the course of the disease to link symptom severity to the level of tylose occlusion and the presence/absence of the bacterial pathogen at fine‐scale resolution. The majority of vessels containing tyloses were devoid of bacterial cells, indicating that direct, localized perception of X. fastidiosa was not a primary cause of tylose formation. In addition, we used X‐ray computed microtomography and machine‐learning to determine that X. fastidiosa induces significant starch depletion in xylem ray parenchyma cells. This suggests that a signalling mechanism emanating from the vessels colonized by bacteria enables a systemic response to X. fastidiosa infection. To understand the transcriptional changes underlying these phenotypes, we integrated global transcriptomics into the phenotypes we tracked over the disease spectrum. Differential gene expression analysis revealed that considerable transcriptomic reprogramming occurred during early PD before symptom appearance. Specifically, we determined that many genes associated with tylose formation (ethylene signalling and cell wall biogenesis) and drought stress were up‐regulated during both Phase I and Phase II of PD. On the contrary, several genes related to photosynthesis and carbon fixation were down‐regulated during both phases. These responses correlate with significant starch depletion observed in ray cells and tylose synthesis in vessels.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Redox regulation of m 6 A methyltransferase METTL3 in β-cells controls the innate immune response in type 1 diabetes

Type 1 Diabetes (T1D) is characterized by the destruction of pancreatic ß-cells. Several observations have renewed the interest in ß-cell RNA sensors and editors. Here, in this study, we report that N 6 -methyladenosine (m 6 A) is an adaptive ß-cell safeguard mechanism that controls the amplitude and duration of the antiviral innate immune response at T1D onset. m 6 A writer methyltransferase 3 (METTL3) levels increase drastically in ß-cells at T1D onset but rapidly decline with disease progression. m 6 A-sequencing revealed the m 6 A hypermethylation of several key innate immune mediators including OAS1, OAS2, OAS3, and ADAR1 in human islets and EndoC-ßH1 cells at T1D onset. METTL3 silencing enhanced OAS levels by increasing its mRNA stability. Consistently, in vivo gene therapy, to prolong Mettl3 overexpression specifically in ß-cells, delayed diabetes progression in the non-obese diabetic (NOD) mouse model of T1D. Mechanistically, the accumulation of reactive oxygen species blocked upregulation of METTL3 in response to cytokines, while physiological levels of nitric oxide enhanced its expression. Furthermore, for the first time to our knowledge, we report that the cysteines in position C276 and C326 in the zinc finger domains of the METTL3 protein are sensitive to S-nitrosylation (SNO) and are significant for the METTL3-mediated regulation of OAS mRNA stability in human ß-cells. Collectively, we report that m 6 A regulates ß-cells to control the innate immune response during the onset of T1D in humans.

2'-5'-oligoadenylate synthetase↗
DOE OSTI2022

Dynamic Frequency Regulation Improvement in Hydropower-Hybrid System using Variational Mode Decomposition

Providing frequency response, especially fast frequency response such as Red D in the Pennsylvania-New Jersey-Maryland Interconnection (PJM) market, is challenging for many generation plants to deliver on their own. If they have adequate flexibility, hydropower plants are typically able to provide slower regulation support (e.g., Reg A in PJM), but do not respond fast enough to provide Reg D. The ability to provide Reg D would improve their revenue because this service is typically more valuable. This work presents a control approach to use hydropower, battery, and ultracapacitor systems to provide fast regulation in a way that uses the response contribution of each asset. In particular, the proposed control architecture applies a variational mode decomposition (VMD) technique on the incoming Reg D signal to extract multiple dynamic-regulation components with non-overlapping frequencies. With the response-speed dependent alignment, these regulation components are fed to the hydrogenator and hybrid energy storage system (HESS). The paper evaluates the proposed approach on a direct-current (DC)-coupled active system by computing several performance measures and analyzing sensitivity based on HESS component proportional capacities. The results reveal that the proposed VMD-based signal conditioning performs well and that optimizing the sizing of the battery and ultracapacitor components further enhances performance.

13 HYDRO ENERGY↗
DOE OSTI2022

Evolutionary analysis of the LORELEI gene family in plants reveals regulatory subfunctionalization

Abstract A signaling complex comprising members of the LORELEI (LRE)-LIKE GPI-anchored protein (LLG) and Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) families perceive RAPID ALKALINIZATION FACTOR (RALF) peptides and regulate growth, reproduction, immunity, and stress responses in Arabidopsis (Arabidopsis thaliana). Genes encoding these proteins are members of multigene families in most angiosperms and could generate thousands of signaling complex variants. However, the links between expansion of these gene families and the functional diversification of this critical signaling complex as well as the evolutionary factors underlying the maintenance of gene duplicates remain unknown. Here, we investigated LLG gene family evolution by sampling land plant genomes and explored the function and expression of angiosperm LLGs. We found that LLG diversity within major land plant lineages is primarily due to lineage-specific duplication events, and that these duplications occurred both early in the history of these lineages and more recently. Our complementation and expression analyses showed that expression divergence (i.e. regulatory subfunctionalization), rather than functional divergence, explains the retention of LLG paralogs. Interestingly, all but one monocot and all eudicot species examined had an LLG copy with preferential expression in male reproductive tissues, while the other duplicate copies showed highest levels of expression in female or vegetative tissues. The single LLG copy in Amborella trichopoda is expressed vastly higher in male compared to in female reproductive or vegetative tissues. We propose that expression divergence plays an important role in retention of LLG duplicates in angiosperms.

Plant Sciences↗
NASA NTRS1990

Minimum-size design of regulation systems and the application to Space Station

A method is proposed to determine the sizes of the regulator and observer and to design the feedback and Kalman gain matrices for the reduced system. The sizes determined are minimum in the sense of satisfying the specified eigenvalue limits when the interaction between the regulator and the observer can be neglected. The resulting sizes will depend on the properties of the original system and the desired response. If the interaction between the regulator and the observer becomes substantial, more modes in the observer should be included, or other methods should be used for reducing the observation spillover or control spillover.

Reddy, A. S. S. R.↗
NASA NTRS1986

Characterization of nucleoside triphosphatase activity in isolated pea nuclei and its photoreversible regulation by light

A nucleoside triphosphatase (NTPase) present in highly purified preparations of pea nuclei was partially characterized. The activity of this enzyme was stimulated by divalent cations (Mg2+ = Mn2+ > Ca2+), but was not affected by the monovalent cations, Na+ and K+. The Mg(2+)-dependent activity was further stimulated by concentrations of Ca2+ in the low micromolar range. It could catalyze the hydrolysis of ATP, GTP, UTP, and CTP, all with a pH optimum of 7.5. The nuclear NTPase activity was not inhibited by vanadate, oligomycin, or nitrate, but was inhibited by relatively low concentrations of quercetin and the calmodulin inhibitor, compound 48/80. The NTPase was stimulated more than 50% by red light, and this effect was reversed by subsequent irradiation with far-red light. The photoreversibility of the stimulation indicated that the photoreceptor for this response was phytochrome, an important regulator of photomorphogenesis and gene expression in plants.

NASA Discipline Plant Biology↗
DOE OSTI2023

An IRE1-proteasome system signalling cohort controls cell fate determination in unresolved proteotoxic stress of the plant endoplasmic reticulum

Excessive accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, which is an underlying cause of major crop losses and devastating human conditions. Here, ER proteostasis surveillance is mediated by the conserved master regulator of the unfolded protein response (UPR), Inositol Requiring Enzyme 1 (IRE1), which determines cell fate by controlling pro-life and pro-death outcomes through as yet largely unknown mechanisms. Here we report that Arabidopsis IRE1 determines cell fate in ER stress by balancing the ubiquitin–proteasome system (UPS) and UPR through the plant-unique E3 ligase, PHOSPHATASE TYPE 2CA (PP2CA)-INTERACTING RING FINGER PROTEIN 1 (PIR1). Indeed, PIR1 loss leads to suppression of pro-death UPS and the lethal phenotype of an IRE1 loss-of-function mutant in unresolved ER stress in addition to activating pro-survival UPR. Specifically, in ER stress, PIR1 loss stabilizes ABI5, a basic leucine zipper (bZIP) transcription factor, that directly activates expression of the critical UPR regulator gene, bZIP60, triggering transcriptional cascades enhancing pro-survival UPR. Collectively, our results identify new cell fate effectors in plant ER stress by showing that IRE1’s coordination of cell death and survival hinges on PIR1, a key pro-death component of the UPS, which controls ABI5, a pro-survival transcriptional activator of bZIP60.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2006

Stress, and pathogen response gene expression in modeled microgravity

Purpose: Immune suppression in microgravity has been well documented. With the advent of human exploration and long-term space travel, the immune system of the astronaut must be optimally maintained. It is important to investigate the expression patterns of cytokine genes, because they are directly related to immune response. Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in the cells of every life form. These proteins are induced when a cell responds to stressors such as heat, cold and oxygen deprivation. Microgravity is another stressor that may regulate HSPs. Heat shock proteins trigger immune response through activities that occur both inside the cell (intracellular) and outside the cell (extracellular). Knowledge about these two gene groups could lead to establishment of a blueprint of the immune response and adaptation-related genes in the microgravity environment. Methods: Human peripheral blood cells were cultured in 1g (T flask) and modeled microgravity (MMG, rotating-wall vessel) for 24 and 72 hours. Cell samples were collected and subjected to gene array analysis using the Affymetrix HG_U95 array. Data was collected and subjected to a two-way analysis of variance. The genes related to immune and stress responses were analyzed. Results and Conclusions: HSP70 was up-regulated by more than two fold in microgravity culture, while HSP90 was significantly down-regulated. HSP70 is not typically expressed in all kinds of cells, but it is expressed at high levels in stress conditions. HSP70 participates in translation, protein translocation, proteolysis and protein folding, suppressing aggregation and reactivating denatured proteins. Increased serum HSP70 levels correlate with a better outcome for heat-stroke or severe trauma patients. At the same time, elevated serum levels of HSP70 have been detected in patients with peripheral or renal vascular disease. HSP90 has been identified in the cytosol, nucleus and endoplasmic reticulum, and exists in many tissue types. HSP90 associates with actin filaments in certain conditions and aids cell motility. The down-regulation of HSP90 could lead to deleterious effects in the lymphocytes, thereby contributing to suppressed immune function in microgravity. Interleukins such as IL 1 alpha, IL11 receptor chain alpha, IL7R, and IL4R were significantly down regulated in modeled microgravity. Further analysis of the genes involved in immune response at the protein level may provide a basis for prophylactic and countermeasure strategies to augment the human immune system for space exploration.

Sundaresan, Alamelu↗
DOE OSTI2021

An economic assessment of behind-the-meter photovoltaics paired with batteries on the Hawaiian Islands.

Due to natural variability and uncertainty, the ever-increasing penetration of solar generation in Hawaii presents challenges to power grid operators to maintain reliable system operation. Demand response (DR) has the potential to be a cost-effective tool for Hawaii to reach its aggressive renewable energy goals while maintaining the reliability of power grids. The Hawaii Public Utilities Commission has approved the Hawaiian Electric Company's revised portfolio of DR programs. The companies have released a grid services purchase agreement and subscribed an initial tranche of load into their DR programs. This paper presents innovative analytical methods and comprehensive economic assessment for distributed photovoltaics (PV) paired with battery energy storage systems (BESSs) for two new DR programs, including fast frequency response and capacity grid service. Optimal dispatch and sizing methods are proposed for the paired system considering different tariff schedules and PV compensation programs across five islands. It was found that while the best resource configuration and potential economic benefits vary with tariff structure, a BESS paired with PV can be optimally dispatched to generate multiple value streams simultaneously. Compensation from DR programs is an important value stream to help increase the cost-effectiveness of the integrated system.

Battery energy storage system↗
NASA NTRS1984

Calcium elicited asymmetric auxin transport in gravity influenced root segments

Auxin is a prime candidate for regulating and modulating the differential growth response of primary corn roots to gravity. Auxin, indole-3-acetic acid (IAA), both promotes and inhibits root elongation rapidly within a narrow concentration range. Thus growth regulation would require only small changes in the short lag period for initiation of gravitropism. Since auxin is transported to/through the zone of elongation toward the meristem, it may serve as a direct communication link between the zone of elongation, site of gravitropic response, and the root cap (RC), site of gravity perception. When auxin transport is inhibited, gravitropism is also inhibited. Napthylpthalamic acid (NPA) is one such inhibitor. It inhibits gravitropism only when applied to the apical growing and dividing region of the root. Application at the basal end of the root does not influence gravitropic NPA causes upward curvature when applied to the upper surface of horizontal, two day-old, intact corn roots. This effect is countered by application of IAA to the opposite side.

Edwards, K. L.↗
DOE OSTI2021

Autocrine and paracrine interferon signalling as ‘ring vaccination’ and ‘contact tracing’ strategies to suppress virus infection in a host

The innate immune response, particularly the interferon response, represents a first line of defence against viral infections. The interferon molecules produced from infected cells act through autocrine and paracrine signalling to turn host cells into an antiviral state. Although the molecular mechanisms of IFN signalling have been well characterized, how the interferon response collectively contribute to the regulation of host cells to stop or suppress viral infection during early infection remain unclear. Here, we use mathematical models to delineate the roles of the autocrine and the paracrine signalling, and show that their impacts on viral spread are dependent on how infection proceeds. In particular, we found that when infection is well-mixed, the paracrine signalling is not as effective; by contrast, when infection spreads in a spatial manner, a likely scenario during initial infection in tissue, the paracrine signalling can impede the spread of infection by decreasing the number of susceptible cells close to the site of infection. Furthermore, we argue that the interferon response can be seen as a parallel to population-level epidemic prevention strategies such as ‘contact tracing’ or ‘ring vaccination’. Thus, our results here may have implications for the outbreak control at the population scale more broadly.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Molecular pathways for learning in the single-cell Stentor coeruleus

The single-cell Stentor coeruleus contracts in response to mechanical taps but habituates and learns to ignore the taps after repeated stimulation. Here, we explored the molecular changes that occur during the formation of this cellular memory in order to improve our understanding of non-synaptic learning. We impaired cellular protein synthesis with cycloheximide and puromycin and found that, contrary to the effects of such treatments on metazoa, these drugs accelerate habituation and prolong memory retention in Stentor . Exploratory proteomic and transcriptomic analyses identified candidate proteins and genes that changed over the course of habituation and response recovery, pointing toward the regulation of Stentor learning by calcium signaling and protein phosphorylation. Building on these results, we found that using RNA interference to knock down the calcium-binding, EF-hand domain-containing protein SteCoe_6763 accelerated habituation. Furthermore, increased extracellular calcium improved Stentor learning, while treatment with kinase and phosphatase inhibitors impaired learning. In particular, KN-93, a drug known to inhibit calcium/calmodulin-dependent kinase II and voltage-gated calcium channels, decreased both the rate and extent of habituation in Stentor , similar to its effects on learning in metazoa. We also discovered that habituation memory can be maintained in progeny following cell division. Taken together, these results suggest that response recovery in Stentor requires new protein synthesis and that memory formation involves the modification of delocalized mechanoreceptors by phosphorylation and calcium signaling. This is consistent with our previous model of Stentor learning, in which habituation occurs through the inactivation of cell-surface receptors.

CaMKII↗
DOE OSTI2020

Transcriptomic Profiles of Zymomonas mobilis 8b to Furfural Acute and Long-Term Stress in Both Glucose and Xylose Conditions

Zymomonas mobilis 8b is an ethanologenic bacterium engineered to utilize both glucose and xylose. The impacts of lignocellulosic hydrolyzate inhibitors on the growth of Zymomonas mobilis 8b have been investigated. However, the molecular responses of these inhibitors have not been completely elucidated yet. In this study, molecular responses to furfural were investigated using transcriptomic approaches of both chip-based microarray and a directional mRNA-Seq. Furfural acute shock time-course experiment with 3 g/L furfural supplemented when cells reached exponential phase and stress response experiment in the presence of 2 g/L furfural from the beginning of fermentation were carried out to study the physiological and transcriptional profiles of short-term and long-term effects of furfural on 8b. Furfural negatively affected 8b growth in terms of final biomass and the fermentation time. Transcriptomic studies indicated that the response of 8b to furfural was dynamic and complex, and differences existed between short-term shock and long-term stress responses. However, the gene function categories were similar with most down-regulated genes related to translation and biosynthesis, while the furfural up-regulated genes were mostly related to general stress responses. Several gene candidates have been identified and genetic studies indicated that expression of ZMO0465 and cysteine synthase operon ZMO0003-0006 driven by its native promoter in a shuttle vector enhanced the furfural tolerance of 8b. In addition, the relationship between microarray and mRNA-Seq was compared with good correlations. The directional mRNA-Seq data not only provided the gene expression profiling, but also can be applied for transcriptional architecture improvement to identify and confirm operons, novel transcripts, hypothetical gene functions, transcriptional start sites, and promoters with different strength.

09 BIOMASS FUELS↗
NASA NTRS2017

Osteogenic Transcription Regulated by Exaggerated Stretch Loading via Convergent Wnt Signaling

Cell and animal studies conducted onboard the International Space Station and formerly the Shuttle flights have provided data illuminating the deleterious biological response of bone to mechanical unloading. Down regulation of proliferative mechanisms within stem cell populations of the osteogenic niche is a suggested mechanism for loss of bone mass. However the intercellular communicative cues from osteoblasts and osteocytes in managing stem cell proliferation and osteogenic differentiation are largely unknown. In this investigation, MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells, are co-culture under dynamic tensile conditions and evaluated for phenotypic expression of biochemical signaling proteins influential in driving stem cell differentiation. MLO-Y4 and MC3T3-E1 were co-cultured on polyethersulfone membrane with a 0.45m porosity to permit soluble factor transfer and direct cell-cell gap junction signaling. Cyclic tensile stimulation was applied for 48 h at a frequency of 0.1Hz and strain of 0.1. Total Live cell counts indicate mechanical activation of MC3T3-E1s inhibits proliferation while MLO-Y4s increase in number. However, the percent of live MLO-Y4s within the population is low (46.3 total count, *p0.05, n4) suggesting a potential apoptotic signaling cascade. Immunofluorescence demonstrated that stimulation of co-cultures elicits increased gap junction communication. Previously reported PCR evaluation of osteogenic markers further corroborate that the co-cultured populations communicative networks play a role in translating mechanical signals to molecular messaging. These findings suggest that an osteocyte-osteoblast signaling feedback mechanism may regulate mechanotransduction of an apoptotic cascade within osteocytes and transcription of cytokine signaling proteins responsible for stem cell niche recruitment much more directly than previously believed.

mechanical stimulation↗
NASA NTRS1999

Ethylene plays multiple nonprimary roles in modulating the gravitropic response in tomato

Ethylene is known to interact with auxin in regulating stem growth, and yet evidence for the role of ethylene in tropic responses is contradictory. Our analysis of four mutants of tomato (Lycopersicon esculentum) altered in their response to gravity, auxin, and/or ethylene revealed concentration-dependent modulation of shoot gravitropism by ethylene. Ethylene inhibitors reduce wild-type gravicurvature, and extremely low (0.0005-0.001 microliter L-1) ethylene concentrations can restore the reduced gravitropic response of the auxin-resistant dgt (diageotropica) mutant to wild-type levels. Slightly higher concentrations of ethylene inhibit the gravitropic response of all but the ethylene-insensitive nr (never-ripe) mutant. The gravitropic responses of nr and the constitutive-response mutant epi (epinastic) are slightly and significantly delayed, respectively, but otherwise normal. The reversal of shoot gravicurvature by red light in the lz-2 (lazy-2) mutant is not affected by ethylene. Taken together, these data indicate that, although ethylene does not play a primary role in the gravitropic response of tomato, low levels of ethylene are necessary for a full gravitropic response, and moderate levels of the hormone specifically inhibit gravicurvature in a manner different from ethylene inhibition of overall growth.

Non-NASA Center↗
DOE OSTI2021

Proline hydroxylase domain-containing enzymes regulate calcium levels in cardiomyocytes by TRPA1 ion channel

Highlights: • PHD induces calcium release from cardiomyocytes through ryanodine channel. • PHD activates TRPA1 to induce extracellular calcium ions into the cell and further activate the ryanodine channel. • TRPA1 is involved in the regulation of PHD-Ca2+-AMPK signaling pathway. The proline hydroxylase domain-containing enzymes (PHDs) acts as cellular oxygen sensors, inducing a series of responses to hypoxia, especially during the regulation of metabolism and energy homeostasis. The increase of Ca{sup 2+} in cardiomyocytes, induced by the opening of PHD signaling pathway, is the key initiation signal necessary for the PHD-mediated regulation of the energy metabolism pathway, but the underlying molecular mechanism remains incompletely understood. This study used PHD inhibitors (PHIs) and PHD2-specific RNA interference (PHD2shRNA) to inhibit PHD signals in cardiomyocytes to explore whether transient receptor potential ankyrin 1 (TRPA1) is involved in the regulation of calcium ion influx in the PHD activation pathway associated with to AMP-activated protein kinase (AMPK). The Fluo-3AM probe was used to measure changes in free intracellular calcium ion concentrations, and Western blot analysis was used to detect the levels of phosphorylated (P)-AMPK, TRPA1, and P–Ca{sup 2+}/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) levels. The PHI-mediated inhibition of PHD resulted in an increase in free Ca{sup 2+} fluorescence in cardiomyocytes, which activated AMPK, TRPA1, and CaMKⅡ. The TRPA1 inhibitor HC030031, the CaMKII inhibitor KN93, and a ryanodine inhibitor (Ryanodine) were all able to inhibit the PHI-induced increase in intracellular Ca{sup 2+} and AMPK activation. Both PHIs and PHD2shRNA were able to effectively activate CaMKII and TRPA1. However, an inositol 1,4,5-triphosphate receptor (IP3R) inhibitor and the protein kinase A (PKA) inhibitor H89 did not significantly inhibit the PHI-induced increase in intracellular Ca{sup 2+} and AMPK activation. These results indicated that PHD might activate the CaMKⅡ pathway through the TRPA1 ion channel, inducing the release of calcium from the sarcoplasmic reticulum through ryanodine receptor 2 (RyR2), activating AMPK to initiate the protective effects of hypoxia in cardiomyocytes.

60 APPLIED LIFE SCIENCES↗