ArticleJournal of molecular and cellular cardiology2010
Ca(2+)/calmodulin-dependent protein kinase II contributes to intracellular pH recovery from acidosis via Na(+)/H(+) exchanger activation.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 55 citations in OpenAlex.
- SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism.Nature reviews. Cardiology · 2023Review
- A Mango Leaf Extract (ZynamiteNutrients · 2023Article
- Direct cardiac effects of SGLT2 inhibitors.Cardiovascular diabetology · 2022Review
- Antiarrhythmic effects and mechanisms of sodium-glucose cotransporter 2 inhibitors: A mini review.Frontiers in cardiovascular medicine · 2022Review
- Cardioprotection by SGLT2 Inhibitors-Does It All Come Down to NaInternational journal of molecular sciences · 2021Review
- Role of Genetic Mutations of the NaMolecular and cellular biochemistry · 2021Review
- CaMKIIδ Splice Variants in the Healthy and Diseased Heart.Frontiers in cell and developmental biology · 2021Review
- Computational Approach for Structural Feature Determination of Grapevine NHX Antiporters.BioMed research international · 2019Article
- NaThe Journal of physiology · 2017Article
- The Na+/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension.Physiological reports · 2016Article
- Article
- Chasing cardiac physiology and pathology down the CaMKII cascade.American journal of physiology. Heart and circulatory physiology · 2015Review
- The cGMP/PKG pathway as a common mediator of cardioprotection: translatability and mechanism.British journal of pharmacology · 2015Review
- Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation.Cell communication and signaling : CCS · 2014Article
- The role of CaMKII regulation of phospholamban activity in heart disease.Frontiers in pharmacology · 2014Review
- CaMKII-dependent responses to ischemia and reperfusion challenges in the heart.Frontiers in pharmacology · 2014Review
- CaMKII-dependent regulation of cardiac Na(+) homeostasis.Frontiers in pharmacology · 2014Review
- Analysis of Ca2+ signaling motifs that regulate proton signaling through the Na+/H+ exchanger NHX-7 during a rhythmic behavior in Caenorhabditis elegans.The Journal of biological chemistry · 2013Article
- Platelet-activating factor stimulates sodium-hydrogen exchange in ventricular myocytes.American journal of physiology. Heart and circulatory physiology · 2011Article
- Translocation of the Na+/H+ exchanger 1 (NHE1) in cardiomyocyte responses to insulin and energy-status signalling.The Biochemical journal · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The Na(+)/H(+) exchanger (NHE-1) plays a key role in pH(i) recovery from acidosis and is regulated by pH(i) and the ERK1/2-dependent phosphorylation pathway. Since acidosis increases the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in cardiac muscle, we examined whether CaMKII activates the exchanger by using pharmacological tools and highly specific genetic approaches. Adult rat cardiomyocytes, loaded with the pH(i) indicator SNARF-1/AM were subjected to different protocols of intracellular acidosis. The rate of pH(i) recovery from the acid load (dpH(i)/dt)-an index of NHE-1 activity in HEPES buffer or in NaHCO(3) buffer in the presence of inhibition of anion transporters-was significantly decreased by the CaMKII inhibitors KN-93 or AIP. pH(i) recovery from acidosis was faster in CaMKII-overexpressing myocytes than in overexpressing beta-galactosidase myocytes (dpH(i)/dt: 0.195+/-0.04 vs. 0.045+/-0.010 min(-)(1), respectively, n=8) and slower in myocytes from transgenic mice with chronic cardiac CaMKII inhibition (AC3-I) than in controls (AC3-C). Inhibition of CaMKII and/or ERK1/2 indicated that stimulation of NHE-1 by CaMKII was independent of and additive to the ERK1/2 cascade. In vitro studies with fusion proteins containing wild-type or mutated (Ser/Ala) versions of the C-terminal domain of NHE-1 indicate that CaMKII phosphorylates NHE-1 at residues other than the canonical phosphorylation sites for the kinase (Ser648, Ser703, and Ser796). These results provide new mechanistic insights and unequivocally demonstrate a role of the already multifunctional CaMKII on the regulation of the NHE-1 activity. They also prove clinically important in multiple disorders which, like ischemia/reperfusion injury or hypertrophy, are associated with increased NHE-1 and CaMKII.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.