2025
472. Role of Voltage-Gated Calcium Channels in Vulnerable Pyramidal Neurons in Primate Dorsolateral Prefrontal Cortex: Elucidating the Role of Cav3.1 and Cav1.2 in Higher-Order Cognition
Datta D, Yang S, Gonzalez-Burgos G, Enwright J, Arion D, Lewis D, Wang M, Arnsten A. 472. Role of Voltage-Gated Calcium Channels in Vulnerable Pyramidal Neurons in Primate Dorsolateral Prefrontal Cortex: Elucidating the Role of Cav3.1 and Cav1.2 in Higher-Order Cognition. Biological Psychiatry 2025, 97: s291-s292. DOI: 10.1016/j.biopsych.2025.02.710.Peer-Reviewed Original ResearchCACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left‐Right Patterning in Xenopus tropicalis
Kostiuk V, Kabir R, Akbari R, Rushing A, González D, Kim A, Kim A, Zenisek D, Khokha M. CACNA1G, A Heterotaxy Candidate Gene, Plays a Role in Ciliogenesis and Left‐Right Patterning in Xenopus tropicalis. Genesis 2025, 63: e70009. PMID: 40008628, PMCID: PMC11867209, DOI: 10.1002/dvg.70009.Peer-Reviewed Original ResearchConceptsCongenital heart diseaseCACNA1GLow-voltage-activated calcium channelsExpression of Cacna1gCalcium channelsPatient cohortCardiac functionLR patterningHeterotaxyLR organizerChannel familyCACNA1SHeart diseaseLeft-rightG expressionXenopus tropicalisAbnormal expressionProcess of cilia formationCardiac loopingMultiple organsSignaling cascadesLR asymmetryPatientsT-typeEmbryonic developmentExploring Calcium Channels as Potential Therapeutic Targets in Blast Traumatic Brain Injury
Wachtler N, O’Brien R, Ehrlich B, McGuone D. Exploring Calcium Channels as Potential Therapeutic Targets in Blast Traumatic Brain Injury. Pharmaceuticals 2025, 18: 223. PMID: 40006037, PMCID: PMC11859800, DOI: 10.3390/ph18020223.Peer-Reviewed Original ResearchCalcium signalingCalcium channelsTherapeutic strategiesCalcium homeostasisFunction of calcium channelsDysregulated calcium signalingModulation of injuryTraumatic brain injuryBrain injuryLoss of calcium homeostasisBlast-related traumatic brain injuryDevelopment of neuroprotective interventionsIntracellular calcium dynamicsPlasma membrane stabilityExtracellular calciumBlast traumatic brain injuryPreclinical modelsTherapeutic outcomesNeuroprotective interventionsMembrane abnormalitiesPharmacological inhibitorsNeuronal somataExclusion criteriaCalcium dynamicsSecondary injury
2024
Ion channels in osteoarthritis: emerging roles and potential targets
Zhou R, Fu W, Vasylyev D, Waxman S, Liu C. Ion channels in osteoarthritis: emerging roles and potential targets. Nature Reviews Rheumatology 2024, 20: 545-564. PMID: 39122910, DOI: 10.1038/s41584-024-01146-0.Peer-Reviewed Original ResearchIon channelsVoltage-dependent calcium channelsAcid-sensing ion channelsTransient receptor potential channelsVoltage-gated sodium channelsIon channel modulatorsFunction of ion channelsPotential clinical applicationsCalcium channelsPreclinical studiesClinical impactSymptomatic reliefPotassium channelsChloride channelsDisease-modifying treatmentsClinical trialsSodium channelsBone hyperplasiaChannel modulationIon channel biologySynovial inflammationClinical applicationPiezo channelsModel of OAPotential targetNeutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis
Ogino N, Leite M, Guerra M, Kruglov E, Asashima H, Hafler D, Ito T, Pereira J, Peiffer B, Sun Z, Ehrlich B, Nathanson M. Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis. Journal Of Clinical Investigation 2024, 134: e171691. PMID: 38916955, PMCID: PMC11324315, DOI: 10.1172/jci171691.Peer-Reviewed Original ResearchAlcohol-associated hepatitisReduced cell proliferationCalcium channel expressionCalcium signaling mechanismsIntracellular calcium channelsCell proliferationRegulate calcium signalingNeutrophil extracellular trapsChannel expressionNeutrophil granule proteinsCalcium channelsNeutrophil infiltrationPatient specimensGranule proteasesMouse modelHealthy subjectsLiver diseaseExtracellular trapsCalcium signalingSerpin E2NeutrophilsElastase activityHepatitisTissue remodelingSignaling mechanismsCalcium signalling and transport in the kidney
Staruschenko A, Alexander R, Caplan M, Ilatovskaya D. Calcium signalling and transport in the kidney. Nature Reviews Nephrology 2024, 20: 541-555. PMID: 38641658, PMCID: PMC12036682, DOI: 10.1038/s41581-024-00835-z.Peer-Reviewed Original ResearchCalcium channelsCalcium levelsCalcium-binding proteinSerum calcium levelsOptimal bone mineralizationPolycystic kidney diseaseIntracellular signaling mechanismsIntracellular second messengersRegulate calcium levelsCalcium handlingSevere complicationsFiltered calciumKidney diseaseCalcium transportRenal cellsCalcium homeostasisCalcium signalingFormation of kidney stonesCalcium dysregulationPhysiological stimuliKidney stonesBone mineralizationKidneySecond messengersSignaling mechanisms283 Decoding Mechanotransduction in Spinal Pseudoarthrosis: A Mouse Model of Spinal Fusion for Developing Mechanosensitive Osteobiologics
Connolly I, Burns R, Kiapour A, Phan D, Esposito E, Kahle K, Shin J, Hadzipasic M, Shankar G. 283 Decoding Mechanotransduction in Spinal Pseudoarthrosis: A Mouse Model of Spinal Fusion for Developing Mechanosensitive Osteobiologics. Neurosurgery 2024, 70: 80-80. DOI: 10.1227/neu.0000000000002809_283.Peer-Reviewed Original ResearchFusion surgerySpinal fusionFusion bedWeek 4Mouse spinePiezo-1Bone formationSpinal fusion surgeryEvidence of bone fusionIliac crest allograftPA tissuesLoss of osteocytesMouse micro-CT imagesMechanosensitive calcium channelsCalcium channelsSpinal pseudoarthrosisCT scanMouse modelPiezo1-dependent mannerBone fusionPseudoarthrosisNormal spineHistological characterizationCT imagesPromote arthrodesisA multi-ancestry genetic study of pain intensity in 598,339 veterans
Toikumo S, Vickers-Smith R, Jinwala Z, Xu H, Saini D, Hartwell E, Pavicic M, Sullivan K, Xu K, Jacobson D, Gelernter J, Rentsch C, Stahl E, Cheatle M, Zhou H, Waxman S, Justice A, Kember R, Kranzler H. A multi-ancestry genetic study of pain intensity in 598,339 veterans. Nature Medicine 2024, 30: 1075-1084. PMID: 38429522, PMCID: PMC12105102, DOI: 10.1038/s41591-024-02839-5.Peer-Reviewed Original ResearchPain intensityChronic painTreat chronic painCalcium channel blockersCross-ancestry meta-analysisGenome-wide association studiesExperience of painSamples of European ancestryPain phenotypesFunctional genomics dataGABAergic neuronsCalcium channelsAnalgesic effectB-blockersDrug groupMillion Veteran ProgramPainSubstance use disordersQuality of lifeDrug repurposing analysisOpioid crisisGenetic architectureCausal genesGenetic lociGenomic dataHRAS-Mutant Cardiomyocyte Model of Multifocal Atrial Tachycardia
Rodríguez N, Patel N, Dariolli R, Ng S, Aleman A, Gong J, Lin H, Rodríguez M, Josowitz R, Sol-Church K, Gripp K, Lin X, Song S, Fishman G, Sobie E, Gelb B. HRAS-Mutant Cardiomyocyte Model of Multifocal Atrial Tachycardia. Circulation Arrhythmia And Electrophysiology 2024, 17: e012022. PMID: 38415356, PMCID: PMC11021157, DOI: 10.1161/circep.123.012022.Peer-Reviewed Original ResearchConceptsMultifocal atrial tachycardiaAtrial-like cardiomyocytesHuman induced pluripotent stem cellsAtrial tachycardiaCostello syndromePluripotent stem cellsGain-of-function pathogenic variantsVoltage-gated calcium channelsStem cellsChannel inhibitor ivabradinePacemaker-like activityHuman induced pluripotent stem cell modelsDecreased beating rateIntracellular calcium homeostasisPacemaker-like cellsPluripotent stem cell modelsStem cell modelAutomated patch clampInhibitor ivabradineFunny currentBlocker verapamilCalcium transientsCalcium handlingCalcium channelsGene expression
2023
Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging
Zhou Y, Normandin M, Belov V, Macdonald-Soccorso M, Moon S, Sun Y, Fakhri G, Guehl N, Brugarolas P. Evaluation of trans- and cis-4‑[18F]Fluorogabapentin for Brain PET Imaging. ACS Chemical Neuroscience 2023, 14: 4208-4215. PMID: 37947793, PMCID: PMC11485007, DOI: 10.1021/acschemneuro.3c00593.Peer-Reviewed Original ResearchConceptsNeuropathic painRodent models of neuropathic painSubunit of voltage-dependent calcium channelsModel of neuropathic painTreatment of neuropathic painMetabolite-corrected arterial input functionVoltage-dependent calcium channelsMultilinear analysis 1Brain uptakePET imagingDose of gabapentinOne-tissue compartment modelRegional time-activity curvesAdult rhesus macaquesPlasma protein bindingTime-activity curvesModerate brain uptakeCalcium channelsInjured nerveArterial input functionGabapentinRodent modelsAnticonvulsant medicationBrain PET imagingRhesus macaques
2022
L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities
Nunes E, Addy N. L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities. Neuropharmacology 2022, 224: 109336. PMID: 36414149, PMCID: PMC11215796, DOI: 10.1016/j.neuropharm.2022.109336.Peer-Reviewed Original ResearchConceptsL-type calcium channelsVentral tegmental areaPre-clinical modelsTegmental areaSubstance useLTCC blockersMood disordersCalcium channelsCo-morbid psychiatric diagnosesDA neuronal activityVoltage-gated calcium channelsMood-related behaviorsSubstance use disordersCalcium channel regulationStress-induced plasticityAccumbens pathwayCardiac medicationsDopamine neuronsLTCC subtypesNeuronal activityNeuronal firingUse disordersPsychiatric diagnosisCalcium entryDopamine activityCatSper and Two-Pore channels (TPC) in GtoPdb v.2022.1
Chung J, Clapham D, Garbers D, Grimm C, Ren D. CatSper and Two-Pore channels (TPC) in GtoPdb v.2022.1. IUPHAR/BPS Guide To Pharmacology CITE 2022, 2022 DOI: 10.2218/gtopdb/f70/2022.1.Peer-Reviewed Original ResearchTwo-pore channelsCatSper channelsCatSper subunitsLike subunitsPlasma membraneSperm tailPrinciple pieceCatSperIndividual domainsTPC1TPC3Number of TMGtoPdb v.TPC2SubunitsProteinVoltage-activated calcium channelsPermeant channelsChannel inhibitorsPatch clampCalcium channelsEndosomesMammalsCatSper1LysosomesActivation of the CaMKII-Sarm1-ASK1-p38 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria
Ding C, Wu Y, Dabas H, Hammarlund M. Activation of the CaMKII-Sarm1-ASK1-p38 MAP kinase pathway protects against axon degeneration caused by loss of mitochondria. ELife 2022, 11: e73557. PMID: 35285800, PMCID: PMC8920508, DOI: 10.7554/elife.73557.Peer-Reviewed Original ResearchConceptsMAPK pathwayLoss of mitochondriaMitochondrial defectsUnbiased genetic screenMAP kinase pathwayCell-specific activationTrafficking complexGenetic screenCEBP-1Kinase pathwayUnderlying cellular mechanismsCellular mechanismsL-type voltage-gated calcium channelsMitochondriaVoltage-gated calcium channelsPathwayUNCAxon degenerationCaenorhabditisActivationCalcium channelsFurther analysisTraffickingSuppressesCaMKIIC2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane
Hwang JY, Wang H, Lu Y, Ikawa M, Chung JJ. C2cd6-encoded CatSperτ targets sperm calcium channel to Ca2+ signaling domains in the flagellar membrane. Cell Reports 2022, 38: 110226. PMID: 34998468, PMCID: PMC8857959, DOI: 10.1016/j.celrep.2021.110226.Peer-Reviewed Original ResearchConceptsFlagellar membraneFlagellar membrane targetingC2 domain proteinsCatSper channelsCatSper channel complexMammalian sperm cellsSperm hyperactivated motilityMale fertilityMembrane targetingTrafficking machineryDomain proteinsLoss of functionHyperactivated motilitySpatiotemporal CaChannel assemblyMolecular mechanismsSperm cellsChannel complexFlagellaMotilityC2CD6MembraneCalcium channelsMachineryProtein
2021
Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice
Sadleir K, Popovoic J, Zhu W, Reidel C, Do H, Silverman R, Vassar R. Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice. Current Alzheimer Research 2021, 18: 283-297. PMID: 34259145, PMCID: PMC9527523, DOI: 10.2174/1567205018666210713125333.Peer-Reviewed Original ResearchConceptsVoltagegated calcium channelsPlacebo-treated miceNeuropathic painPregabalin treatmentStatistically significant positive correlationCalcium channelsCalcium influxAb levelsDecreased markersPregabalinSignificant positive correlationCerebral concentrationsEffective treatmentAmyloid depositsCausative roleDystrophyCalcium dysregulationMiceNeuritic dystrophyProgression of amyloid pathologyPathologyImmunofluorescence imagingNeuronal processesPlaqueTreatment
2020
Lamellar cells in Pacinian and Meissner corpuscles are touch sensors
Nikolaev YA, Feketa VV, Anderson EO, Schneider ER, Gracheva EO, Bagriantsev SN. Lamellar cells in Pacinian and Meissner corpuscles are touch sensors. Science Advances 2020, 6: eabe6393. PMID: 33328243, PMCID: PMC7744075, DOI: 10.1126/sciadv.abe6393.Peer-Reviewed Original ResearchLamellar cellsR-type voltage-gated calcium channelsMeissner corpusclesAction potentialsChannel-dependent action potentialsPacinian corpusclesVoltage-gated calcium channelsSensory afferent neuronsNon-neuronal cellsBill skinAfferent neuronsNeuronal afferentsCalcium channelsElectrophysiological recordingsTactile stimuliCorpusclesIon channelsCellsSkinFirst evidenceTactile organsAfferentsNeuronsThe genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex
Arnsten AFT, Datta D, Wang M. The genie in the bottle-magnified calcium signaling in dorsolateral prefrontal cortex. Molecular Psychiatry 2020, 26: 3684-3700. PMID: 33319854, PMCID: PMC8203737, DOI: 10.1038/s41380-020-00973-3.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexCognitive disordersPrefrontal cortexPrimate dorsolateral prefrontal cortexHigher cortical circuitsPrimary visual cortexInternal calcium releaseRisk of schizophreniaAge-related lossLevels of calciumDendritic atrophyAmyloid pathologyCalcium binding proteinInflammatory insultCalcium overloadTau phosphorylationCortical circuitsDendritic spinesNeuronal firingCalcium channelsAssociation cortexSynaptic efficacyVisual cortexAlzheimer's diseaseSpecial molecular mechanismNeutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis
Takeuchi M, Vidigal PT, Guerra MT, Hundt MA, Robert ME, Olave-Martinez M, Aoki S, Khamphaya T, Kersten R, Kruglov E, de la Rosa Rodriguez R, Banales JM, Nathanson MH, Weerachayaphorn J. Neutrophils interact with cholangiocytes to cause cholestatic changes in alcoholic hepatitis. Gut 2020, 70: 342-356. PMID: 33214166, PMCID: PMC7906004, DOI: 10.1136/gutjnl-2020-322540.Peer-Reviewed Original ResearchConceptsBile ductCholestatic changesLimited treatment optionsPresence of cholestasisAbility of neutrophilsLife-threatening diseaseNew therapeutic targetsHuman bile ductIntracellular calcium channelsAlcoholic hepatitisLiver biopsyControl neutrophilsPathological findingsHepatocellular damageHistological findingsTreatment optionsCell adhesion moleculeHistological parametersDisease altersITPR3 expressionTherapeutic targetAnimal modelsCalcium channelsNeutrophilsPatientsReplicated risk CACNA1C variants for major psychiatric disorders may serve as potential therapeutic targets for the shared depressive endophenotype.
Guo X, Fu Y, Zhang Y, Wang T, Lu L, Luo X, Wang K, Huang J, Xie T, Zheng C, Yang K, Tong J, Zuo L, Kang L, Tan Y, Jiang K, Li CR, Luo X. Replicated risk CACNA1C variants for major psychiatric disorders may serve as potential therapeutic targets for the shared depressive endophenotype. 2020, 4 PMID: 34046650, PMCID: PMC8153461.Peer-Reviewed Original ResearchMajor psychiatric disordersGenome-wide association studiesL-type voltage-gated calcium channelsMajor depressive disorderMRNA expression regulationPsychiatric disordersTherapeutic targetBipolar disorderChronic mild stress (CMS) ratsHuman hippocampusExpression regulationDepressive endophenotypeType voltage-gated calcium channelsRole of venlafaxineVoltage-gated calcium channelsPotential therapeutic targetRisk genesSignificant mRNA expressionVenlafaxine treatmentDepressive disorderStress ratsDepressive symptomsIndependent cohortCalcium channelsMRNA expressionDstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles
Hsu IU, Linsley JW, Reid LE, Hume RI, Leflein A, Kuwada JY. Dstac Regulates Excitation-Contraction Coupling in Drosophila Body Wall Muscles. Frontiers In Physiology 2020, 11: 573723. PMID: 33123029, PMCID: PMC7573238, DOI: 10.3389/fphys.2020.573723.Peer-Reviewed Original ResearchExcitation-contraction couplingL-type voltage-gated calcium channelsVoltage-gated calcium channelsSubset of neuronsBody wall musclesL-type CaCalcium channelsNormal expression levelsEC couplingMuscle contractionSkeletal muscleSpecific antibodiesMuscleLarval body wall musclesDmca1DExpression levelsWall musclesNormal locomotionDrosophila body wall musclesNeuronsVertebrate skeletal muscleAntibodiesDeficient larvae
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