Influence of prior Na+pump activity on pump and Na+/Ca2+exchange currents in mouse ventricular myocytes

Su, Zhi; Zou, Anruo; Nonaka, Akihiko; Zubair, Iram; Sanguinetti, Michael C.; Barry, William H.

doi:10.1152/ajpheart.1998.275.5.h1808

Cited by 44 publications

(47 citation statements)

References 30 publications

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“…Calculations that assume complete dialysis of intracellular ionic conditions with the patch pipette filling solution, however, predict E Na-Ca ϭ Ϫ64 mV. As suggested by others (26,55,56), we speculate that NCX, a mediator of substantial ionic flux, alters ionic conditions in subsarcolemmal domains in the vicinity of the exchanger complex. Thus, E Na-Ca may not be accurately predicted based on measurements of bulk Na ϩ and Ca 2ϩ concentrations.…”

Section: Figsupporting

confidence: 51%

Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy

Wang¹,

Nolan²,

Kutschke³

et al. 2001

Journal of Biological Chemistry

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Perturbations of Ca2؉ metabolism are central to the pathogenesis of cardiac hypertrophy. The electrogenic Na ؉ -Ca 2؉ exchanger mediates a substantial component of transmembrane Ca 2؉ movement in cardiac myocytes and is up-regulated in heart failure. However, the role of the exchanger in the pathogenesis of cardiac hypertrophy is poorly understood. Thoracic aortic banding in mice induced 50 -60% increases in heart mass and cardiomyocyte size. Despite the absence of myocardial dysfunction, steady-state NCX1 transcript and protein levels were increased to an extent similar to that reported in heart failure. As recent studies indicate that calcineurin is critical to the expression of Na ؉ -Ca 2؉ exchanger genes, we inhibited calcineurin with cyclosporin. Calcineurin inhibition blunted the increases in NCX1 transcript and protein levels and eliminated the increases in heart mass and cell volume normally associated with pressure overload. To examine the functional significance of these changes, we measured Na ؉ -Ca 2؉ exchanger current in two independent ways. Surprisingly, exchanger current density was decreased in hypertrophied myocytes, and this down-regulation was eliminated by calcineurin inhibition. Together, these data reveal a role for Na ؉ -Ca 2؉ exchanger current in the electrical remodeling of hypertrophy and implicate calcineurin signaling therein. In addition, these data suggest the Na ؉ -Ca 2؉ exchanger is functionally regulated in hypertrophy.

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Section: Figsupporting

confidence: 51%

Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy

Wang¹,

Nolan²,

Kutschke³

et al. 2001

Journal of Biological Chemistry

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“…I NaCa plays an important role in mouse myocyte Ca 2ϩ dynamics (84). The absolute value of I NaCa does not exceed 1.0 pA/pF within the range Ϫ120 to ϩ40 mV.…”

Section: Derivation and Simulation Of Component Currentsmentioning

confidence: 92%

Computer model of action potential of mouse ventricular myocytes

Bondarenko

Szigeti

Bett

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

268

313

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We have developed a mathematical model of the mouse ventricular myocyte action potential (AP) from voltage-clamp data of the underlying currents and Ca2+ transients. Wherever possible, we used Markov models to represent the molecular structure and function of ion channels. The model includes detailed intracellular Ca2+ dynamics, with simulations of localized events such as sarcoplasmic Ca2+ release into a small intracellular volume bounded by the sarcolemma and sarcoplasmic reticulum. Transporter-mediated Ca2+ fluxes from the bulk cytosol are closely matched to the experimentally reported values and predict stimulation rate-dependent changes in Ca2+ transients. Our model reproduces the properties of cardiac myocytes from two different regions of the heart: the apex and the septum. The septum has a relatively prolonged AP, which reflects a relatively small contribution from the rapid transient outward K+ current in the septum. The attribution of putative molecular bases for several of the component currents enables our mouse model to be used to simulate the behavior of genetically modified transgenic mice.

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“…20 Myocyte cross-sectional areas were measured on freshly isolated adult cardiac myocytes using a computerized morphometric system (SigmaScan, Systat Inc). All myocytes were measured at the same magnification with the observer blinded to the genotype of the animals.…”

Section: Myocyte Isolation and Analysismentioning

confidence: 99%

Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis

Xiao

Mao

Baumgarten

et al. 2001

Circulation Research

141

143

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Abstract-c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown.

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Influence of prior Na⁺pump activity on pump and Na⁺/Ca²⁺exchange currents in mouse ventricular myocytes

Cited by 44 publications

References 30 publications

Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy

Na+-Ca2+ Exchanger Remodeling in Pressure Overload Cardiac Hypertrophy

Computer model of action potential of mouse ventricular myocytes

Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis

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