The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH

Lazdunski, Michel; Frelin, Christian; Vigne, Paul

doi:10.1016/s0022-2828(85)80119-x

Cited by 568 publications

(214 citation statements)

References 82 publications

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“…This activates the plasmalemmal Na + /Ca ++ exchanger inducing a deleterious increase of intracellular Ca ++ that triggers various pathways ultimately leading to cell death [74,99,98,77]. Genetic ablation or pharmalogic inhibition of NHE1 during episodes of ischemiareperfusion mitigated cardiac and neural injuries both in vivo and in vitro in rodents and pigs [85,32,62]. Consistent with this, NHE1 overactivity has been linked to cardiac hypertrophy and heart failure [168].…”

Section: Slc9a1-nhe1mentioning

confidence: 74%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

137

122

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The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

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Section: Slc9a1-nhe1mentioning

confidence: 74%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

137

122

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“…The indirect effect could explain some of our results. In normoxia the turnover of Na-H exchange is reduced (Lazdunski et al, 1985;L'Allemain & Pouyssegur, 1987) and this explains the absence of effect of heptaminol on intracellular pH. However, the stimulation of PLC will simultaneously induce an increase in inositol triphosphate (1P3) which is known to activate calcium release from the sarcoplasmic reticulum.…”

Section: Experiments In Ischaemic Heartsmentioning

confidence: 99%

Decrease in internal H ⁺ and positive inotropic effect of heptaminol hydrochloride: a ³¹P n.m.r. spectroscopy study in rat isolated heart

Berthiau

Garnier

Argibay

et al. 1989

British J Pharmacology

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1The cardiotonic effect of heptaminol hydrochloride (Hept-a-myl, Delalande) was studied using 31P-nuclear magnetic resonance (n.m.r.) spectroscopy (LVP). 31P-n.m.r. spectra were recorded every 2 min. Changes in cardiac adenosine triphosphate (ATP), phosphocreatine (PCr) and inorganic phosphate (Pi) were followed and intracellular pH (pHi) was estimated from the chemical shift of Pi. 3 The effects of heptaminol were tested in different conditions: normoxia, moderate ischaemia, severe ischaemia, and moderate ischaemia in the presence of amiloride or guanidinium chloride as inhibitors of the Na-H exchange. 4 In normoxia, heptaminol induced a cyclic increase of systolic LVP, associated with an increase in Pi. No significant effect on pHi was observed. In changing from normoxia to moderate ischaemia, PCr and systolic LVP decreased; a mild intracellular acidification (pHi 6.96) was obtained. Heptaminol induced a restoration of pHi and increased LVP. In severe ischaemia, the realkalinization effect and the restoration of LVP induced by heptaminol were no longer observed. During moderate ischaemia, Na-H exchange inhibitors decreased pHi and LVP. Heptaminol applied in the presence of these inhibitors was unable to restore pHi and LVP. 5.These results suggest that the positive inotropic effect of heptaminol during moderate ischaemia could be related to a restoration of internal pH, possibly mediated by a stimulation of the Na-H exchange.

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“…Ischemia causes intracellular acidification of cardiac myocytes, with reperfusion resulting in restoration of physiologic extracellular pH and creating a H + gradient prompting efflux of H + , with concomitant Na + influx through NHE1. 50 The resultant rise in intracellular Na + then prompts an increase in intracellular Ca 2+ through the Na + /Ca 2+ exchange system. Finally, elevated intracellular Ca 2+ triggers deleterious downstream effects, including initiation of apoptotic pathways.…”

Section: The Structure Of Nhe1mentioning

confidence: 99%

Na⁺/H⁺ Exchange and Hypoxic Pulmonary Hypertension

Huetsch

Shimoda

2015

Pulm. circ.

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Intracellular pH (pH i ) homeostasis is key to the functioning of vascular smooth muscle cells, including pulmonary artery smooth muscle cells (PASMCs). Sodium-hydrogen exchange (NHE) is an important contributor to pH i control in PASMCs. In this review, we examine the role of NHE in PASMC function, in both physiologic and pathologic conditions. In particular, we focus on the contribution of NHE to the PASMC response to hypoxia, considering both acute hypoxic pulmonary vasoconstriction and the development of pulmonary vascular remodeling and pulmonary hypertension in response to chronic hypoxia. Hypoxic pulmonary hypertension remains a disease with limited therapeutic options. Thus, this review explores past efforts at disrupting NHE signaling and discusses the therapeutic potential that such efforts may have in the field of pulmonary hypertension.

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The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH

Cited by 568 publications

References 82 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Decrease in internal H ⁺ and positive inotropic effect of heptaminol hydrochloride: a ³¹P n.m.r. spectroscopy study in rat isolated heart

Na⁺/H⁺ Exchange and Hypoxic Pulmonary Hypertension

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The sodium/hydrogen exchange system in cardiac cells: Its biochemical and pharmacological properties and its role in regulating internal concentrations of sodium and internal pH

Cited by 568 publications

References 82 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Decrease in internal H + and positive inotropic effect of heptaminol hydrochloride: a 31P n.m.r. spectroscopy study in rat isolated heart

Na+/H+ Exchange and Hypoxic Pulmonary Hypertension

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Decrease in internal H ⁺ and positive inotropic effect of heptaminol hydrochloride: a ³¹P n.m.r. spectroscopy study in rat isolated heart

Na⁺/H⁺ Exchange and Hypoxic Pulmonary Hypertension