Na+/K+-pump and neurotransmitter membrane receptors

Pivovarov, A. S.; Calahorro, Fernando; Walker, Robert

doi:10.1007/s10158-018-0221-7

Cited by 120 publications

(80 citation statements)

References 130 publications

(162 reference statements)

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“…19 Serum concentrations of potassium decrease because of insulin stimulation of the Na + /K + ATPase, 16,20 a cell-wall enzyme that is responsible for flux of potassium into the cell and sodium out 18 and is essential in transmission of nerve impulses and contraction of muscles. 21,22 Hypokalemia may then result in impaired transmission of electrical impulses, increasing the risk of potentially lethal cardiac arrhythmias. 23,24 Hypokalemia may also manifest as weakness, hyporeflexia, respiratory depression, and paralysis.…”

Section: Pathophysiology Of Refeeding Syndromementioning

confidence: 99%

ASPEN Consensus Recommendations for Refeeding Syndrome

Silva¹,

et al. 2020

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Introduction In the spring of 2017, the American Society for Parenteral and Enteral Nutrition (ASPEN) Parenteral Nutrition Safety Committee and the Clinical Practice Committee convened an interprofessional task force to develop consensus recommendations for identifying patients with or at risk for refeeding syndrome (RS) and for avoiding and managing the condition. This report provides narrative review and consensus recommendations in hospitalized adult and pediatric populations. Methods Because of the variation in definitions and methods reported in the literature, a consensus process was developed. Subgroups of authors investigated specific issues through literature review. Summaries were presented to the entire group for discussion via email and teleconferences. Each section was then compiled into a master document, several revisions of which were reviewed by the committee. Findings/Recommendations This group proposes a new clinical definition, and criteria for stratifying risk with treatment and screening strategies. The authors propose that RS diagnostic criteria be stratified as follows: a decrease in any 1, 2, or 3 of serum phosphorus, potassium, and/or magnesium levels by 10%–20% (mild), 20%–30% (moderate), or >30% and/or organ dysfunction resulting from a decrease in any of these and/or due to thiamin deficiency (severe), occurring within 5 days of reintroduction of calories. Conclusions These consensus recommendations are intended to provide guidance regarding recognizing risk and identifying, stratifying, avoiding and managing RS. This consensus definition is additionally intended to be used as a basis for further research into the incidence, consequences, pathophysiology, avoidance, and treatment of RS.

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Section: Pathophysiology Of Refeeding Syndromementioning

confidence: 99%

ASPEN Consensus Recommendations for Refeeding Syndrome

Silva¹,

et al. 2020

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“…The α 3 isoform is encoded by the ATP1A3 gene (OMIM #182350) on chromosome 19q13 encodes for the α 3 subunit of the Na+/K+-ATPase, an ubiquitous, electrogenic transmembrane ATPase first described in 1957 51 and located on the cytosolic side of the outer plasma membrane. 52 Exporting 3 Na + and importing 2 K + ions for every single ATP molecule hydrolyzed, the Na + /K + -ATPase maintains the gradient of a higher extracellular Na + concentration and a higher K + intracellular level. 53,54 Although α 3 is the subunit predominantly expressed in neurons, some neurons express α 1that is predominantly expressed in glial cells.…”

Section: Atypical Ahcmentioning

confidence: 99%

<p>Alternating Hemiplegia of Childhood: Understanding the Genotype–Phenotype Relationship of ATP1A3 Variations</p>

Capuano¹,

Garone²,

Tiralongo³

et al. 2020

TACG

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Alternating hemiplegia of childhood (AHC) is a rare neurological disorder affecting children with an onset before 18 months. Diagnostic clues include transient episodes of hemiplegia alternating in the laterality or quadriparesis, nystagmus and other paroxysmal attacks as tonic and dystonic spells. Epilepsy is also a common feature. In the past, a great effort has been done to understand the genetic basis of the disease leading to the discovery of mutations in the ATP1A3 gene encoding for the alpha3 subunit of Na + / K + ATPase, a protein already related to another disease named Rapid Onset Dystonia Parkinsonism (RDP). ATP1A3 mutations account for more than 70% of cases of AHC. In particular, three hotspot mutations account for about 60% of all cases, and these data have been confirmed in large population studies. Specifically, the p.Asp801Asn variant has been found to cause 30-43% of all cases, p.Glu815Lys is responsible for 16-35% of cases and p. Gly947Arg accounts for 8-15%. These three mutations are associated with different clinical phenotype in terms of symptoms, severity and prognosis. In vitro and in vivo models reveal that a crucial role of Na + /K + ATPase pump activity emerges in maintaining a correct membrane potential, survival and homeostasis of neurons. Herein, we attempt to summarize all clinical, genetic and molecular aspects of AHC considering ATP1A3 as its primary disease-causing determinant.

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“…Other studies in the field have demonstrated that these electrophysiological aberrations may be related to intracellular increases in sodium concentration in both the presence of AHC causing mutations and with ion transport inhibition after treatment with pump antagonists (Pivovarov et al, 2018;Tiziano, 2019;Toustrup-Jensen et al, 2014). In collaboration, we recently used iPSC-derived neurons with the G947R mutation to investigate fundamental cellular defects and observed impaired ion pump activity and depolarized resting membrane potentials in AHC mutant neurons (Simmons et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Neuronal Modeling of Alternating Hemiplegia of Childhood Reveals Transcriptional Compensation and Replicates a Trigger-Induced Phenotype

Snow

Westlake

Klofas

et al. 2020

Preprint

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ABSTRACTAlternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by heterozygous de novo missense mutations in the ATP1A3 gene that encodes the neuronal specific α3 subunit of the Na,K-ATPase (NKA) pump. Mechanisms underlying patient episodes including environmental triggers remain poorly understood, and there are no empirically proven treatments for AHC. In this study, we generated patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls for the E815K ATP1A3 mutation that causes the most phenotypically severe form of AHC. Using an in vitro iPSC-derived cortical neuron disease model, we found elevated levels of ATP1A3 mRNA in AHC lines compared to controls, without significant perturbations in protein expression. Microelectrode array analyses demonstrated that in cortical neuronal cultures, ATP1A3+/E815K iPSC-derived neurons displayed a non-significant trend toward less overall activity than neurons differentiated from isogenic mutation-corrected and unrelated control cell lines. However, induction of cellular stress by elevated temperature revealed a hyperactivity phenotype following heat stress in ATP1A3+/E815K lines compared to control lines. Treatment with flunarizine, a drug commonly used to prevent AHC episodes, did not impact this stress-triggered phenotype. These findings support the use of iPSC-derived neuronal cultures for studying complex neurodevelopmental conditions such as AHC and provide a potential route toward future therapeutic screening and mechanistic discovery in a human disease model.

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Na+/K+-pump and neurotransmitter membrane receptors

Cited by 120 publications

References 130 publications

ASPEN Consensus Recommendations for Refeeding Syndrome

ASPEN Consensus Recommendations for Refeeding Syndrome

<p>Alternating Hemiplegia of Childhood: Understanding the Genotype–Phenotype Relationship of ATP1A3 Variations</p>

Neuronal Modeling of Alternating Hemiplegia of Childhood Reveals Transcriptional Compensation and Replicates a Trigger-Induced Phenotype

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