Low extracellular K+ increases intracellular Ca2+ oscillation and injury by activating the reverse mode Na+–Ca2+ exchanger and inhibiting the Na+, K+ ATPase in rat cardiomyocytes

Wu, Feng; Wei, Geng-Ze; Li, Weijie; Liu, Bing; Zhou, Jing‐Jun; Wang, Haichang; Gao, Feng

doi:10.1016/j.ijcard.2008.11.037

Cited by 6 publications

(2 citation statements)

References 29 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ions besides Na + and Ca 2+ participate in regulation of NCX as well. The studies of Feng Wu et al [37] showed that low Ko increased Cai oscillation and injury by activating the reverse-mode NCX and inhibiting the Na + /K + ATPase in rat cardiomyocytes. Compared to controls, myocytes reperfused with low K + had greater number of calcium oscillations and reverse-mode NCX activity, which were accompanied with decreased cell length recovery and cell viability.…”

Section: Conditions Related To Ncx During Irmentioning

confidence: 99%

The Na+/Ca2+ exchanger in cardiac ischemia/reperfusion injury

Chen

2012

Med Sci Monit

View full text Add to dashboard Cite

SummaryThe Na+/Ca2+ exchanger (NCX) is an important electrogenic transporter in maintaining Na+ and Ca2+ homeostasis in a variety of mammalian organs, and is involved in the physiological and pathophysiological regulation of Ca2+ concentration in the myocardium. It can affect cardial structure, electrophysiology and contractile properties. The role of the NCX in heart cells following ischemia/reperfusion (IR) has been investigated using a number of in vitro and in vivo models. During ischemia, ionic disturbances favor Ca2+-influx mode activity as excess Na+ is extruded in exchange for Ca2+, giving rise to increased intracellular Ca2+ levels (Cai). This rise in Cai contributes to reversible cellular dysfunction upon reperfusion, such as myocardial necrosis, arrhythmia, systolic dysfunction and heart failure. We have reviewed the major in vivo and in vitro cardiac IR-related NCX studies in an attempt to clarify the functions of NCX in IR and conclude that recent studies suggest blockage of NCX has potential therapeutic applications. Although the use of different IR models, application of NCX stimulators and inhibitors, and development of NCX transgenic animals do help elucidate the role of this ion exchanger in heart cells, related mechanisms are not completely understood and clinically effective specific NCX inhibitors need further research.

show abstract

Section: Conditions Related To Ncx During Irmentioning

confidence: 99%

The Na+/Ca2+ exchanger in cardiac ischemia/reperfusion injury

Chen

2012

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…The reduction in [Na + ] o is one approach to dampen the ability of the NCX to extrude Ca 2+ . KB-R7943 is also used in other animal models to address a role in the reversal of NCX [57]. The action of KB-R7943 was surprising given that the EPSP amplitudes increased throughout the response train when exposed to this compound.…”

Section: Action Of Kb-r7943 In Compromising Ncxmentioning

confidence: 99%

Actions of NCX, PMCA and SERCA on Short-Term Facilitation and Maintenance of Transmission in Nerve Terminals~!2010-03-10~!2010-08-23~!2010-09-08~!

Desai-Shah¹

2010

TOPHYJ

View full text Add to dashboard Cite

Residual Ca 2+ can accumulate in the nerve terminal during repetitive stimulation; thus, the basis for short-term facilitation (STF). The plasmalemmal Na + /Ca 2+ exchanger [NCX], the Ca 2+-ATPase (PMCA) and the sarcoplasmic/endoplasmic reticulum Ca 2+-ATPase (SERCA) on the endoplasmic reticulum are three important Ca 2+ regulatory processes in controlling [Ca 2+ ] i. The role of these [Ca 2+ ] i regulators in the development and maintenance of STF was addressed at the neuromuscular junction. When the NCX is compromised by reduced [Na + ] o , the EPSP amplitudes decrease, but with KB-R7943 (a reverse blocker of NCX) the amplitude increases. Compromising the PMCA with pH 8.8 produces an increase in EPSP amplitudes, but treatments with carboxyeosin (a blocker of PMCA) produced mixed results. Blocking the SERCA increases EPSP amplitudes. Facilitation was only slighted altered in some conditions with these manipulations. The results support the view that release is not saturated during a plateau phase of STF since the terminal is able to reach a new plateau with higher stimulation frequency or an altered [Ca 2+ ] i. Multiple approaches in compromising the NCX and PMCA are presented. These findings are significant because there is a rapid alteration in transmission when compromising Ca 2+ extrusion mechanisms during STF.

show abstract

Towards Understanding the Role of the Na+-Ca2+ Exchanger Isoform 3

Michel

Hoenderop

Bindels

2015

Reviews of Physiology, Biochemistry and Pharmacology

View full text Add to dashboard Cite

The Na²⁺-Ca²⁺ exchanger (NCX) is critical for Ca²⁺ homeostasis throughout the body. Of the three isoforms in the NCX family, NCX1 has been extensively studied, providing a good basis for understanding the molecular aspects of the NCX family, including structural resemblances, stoichiometry, and mechanism of exchange. However, the tissue expression of the third isoform of the family, NCX3, together with its proposed involvement in the Ca²⁺ fluxes of the endoplasmic reticulum and the mitochondria suggests a distinctive role for this isoform. Investigations of the exchanger revealed the involvement of NCX3 in diverse processes such as bone formation, TNF-α production, slow-twitch muscle contraction, and long-term potentiation in the hippocampus. Furthermore, the study of its posttranslational modification, its cleavage by the Ca²⁺-sensitive protease, calpain, and its upregulation in numerous stress conditions linked NCX3 to the aberrant Ca²⁺ influx seen during neuronal excitotoxicity in Alzheimer's disease, brain stroke, and neuronal injuries. Hence, beyond its role in calcium homeostasis, NCX3 plays an important role in stress conditions, neuronal excitotoxicity, and metabolism and is thereby a key element in many cell types. The present review aims to survey the knowledge on NCX3, focusing on the recent discoveries on its functional and structural properties, and discusses the implications of NCX3 in both physiological and pathological conditions.

show abstract

Low extracellular K+ increases intracellular Ca2+ oscillation and injury by activating the reverse mode Na+–Ca2+ exchanger and inhibiting the Na+, K+ ATPase in rat cardiomyocytes

Cited by 6 publications

References 29 publications

The Na+/Ca2+ exchanger in cardiac ischemia/reperfusion injury

The Na+/Ca2+ exchanger in cardiac ischemia/reperfusion injury

Actions of NCX, PMCA and SERCA on Short-Term Facilitation and Maintenance of Transmission in Nerve Terminals~!2010-03-10~!2010-08-23~!2010-09-08~!

Towards Understanding the Role of the Na+-Ca2+ Exchanger Isoform 3

Contact Info

Product

Resources

About