Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking Na+/K+ Pump As Revealed by Experiments and Simulation

Takeuchi, Ayako; Tatsumi, Shuji; Sarai, Nobuaki; Terashima, Keisuke; Matsuoka, Satoshi; Noma, Akinori

doi:10.1085/jgp.200609646

Cited by 64 publications

(63 citation statements)

References 70 publications

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“…530, , 1018. In some cell types, the plasma membrane Ca 2ϩ -ATPase (PMCA) and the Na ϩ /Ca 2ϩ exchanger (NCX) participate in (976) or, in the case of dog red blood cells (RBCs), are entirely responsible for (768), steady-state maintenance of cell volume.…”

Section: Fundamentals: the Donnan Equilibrium Cell Volume Maintementioning

confidence: 99%

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Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,254

1,677

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The ability to control cell volume is pivotal for cell function. Cell volume perturbation elicits a wide array of signaling events, leading to protective (e.g., cytoskeletal rearrangement) and adaptive (e.g., altered expression of osmolyte transporters and heat shock proteins) measures and, in most cases, activation of volume regulatory osmolyte transport. After acute swelling, cell volume is regulated by the process of regulatory volume decrease (RVD), which involves the activation of KCl cotransport and of channels mediating K+, Cl−, and taurine efflux. Conversely, after acute shrinkage, cell volume is regulated by the process of regulatory volume increase (RVI), which is mediated primarily by Na+/H+exchange, Na+-K+-2Cl−cotransport, and Na+channels. Here, we review in detail the current knowledge regarding the molecular identity of these transport pathways and their regulation by, e.g., membrane deformation, ionic strength, Ca2+, protein kinases and phosphatases, cytoskeletal elements, GTP binding proteins, lipid mediators, and reactive oxygen species, upon changes in cell volume. We also discuss the nature of the upstream elements in volume sensing in vertebrate organisms. Importantly, cell volume impacts on a wide array of physiological processes, including transepithelial transport; cell migration, proliferation, and death; and changes in cell volume function as specific signals regulating these processes. A discussion of this issue concludes the review.

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Section: Fundamentals: the Donnan Equilibrium Cell Volume Maintementioning

confidence: 99%

“…The Na ϩ /Ca 2ϩ exchanger NCX is also activated both by shrinkage and by increases in PtdIns(4,5)P 2 (1106; see Ref. 350), yet is not an RVI effector; conversely, NCX contributes to steady-state net osmolyte extrusion in some cell types (768,976).…”

Section: Phosphoinositide Kinases and Phospholipases C And Dmentioning

confidence: 99%

Physiology of Cell Volume Regulation in Vertebrates

Hoffmann

Lambert²,

Pedersen³

2009

Physiological Reviews

1,254

1,677

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“…As Na + /K + pump has a crucial role in cell adaptation process, aging can be considered as a consequence of Na + /K + pump dysfunction [14,10], which leads to the down regulation Ca 2+ homeostasis [15][16][17][18]. Small enhancement of intracellular Ca 2+ concentration leads to the inactivation of Na…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

Ayrapetyan¹

2012

JBB

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“…Using this model, we proposed the principal ionic mechanisms underlying the spontaneous action potential. In the current study, we revised the model by updating the ion channels and incorporating the mitochondria and β1-adrenergic cascade models described by Matsuoka et al (2004), Terashima et al (2006), Takeuchi et al (2006), and Kuzumoto et al (2007) [3][4][5][6] to analyze the roles of each target ion current, including the L-type Ca 2+ current (I CaL ), the sustained inward current (I st ), the hyperpolarizationactivated cation current (I ha ), and the slow component of the delayed rectifier K + current (I Ks ) in the positive chronotropy during β1-adrenergic stimulation. Our new model also includes an alteration of Ca 2+ dynamics during stimulation by calculating a modification of the Ca 2+ pump (SERCA) on the sarcoplasmic membrane.…”

mentioning

confidence: 99%

Ionic Mechanisms Underlying the Positive Chronotropy Induced by β1-Adrenergic Stimulation in Guinea Pig Sinoatrial Node Cells: a Simulation Study

et al. 2008

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Positive chronotropy induced by β1-adrenergic stimulation is achieved by multiple interactions of ion channels and transporters in sinoatrial node pacemaker cells (SANs). To investigate the ionic mechanisms, we updated our SAN model developed in 2003 and incorporated the β1-adrenergic signaling cascade developed by Kuzumoto et al. (2007). Since the slow component of the delayed rectifier K + current (I Ks ) is one of the major targets of the β1-adrenergic cascade, we developed a guinea pig model with a large I Ks . The new model provided a good representation of the experimental characteristics of SANs. A comparison of individual current during diastole recorded before and after β1-adrenergic stimulation clearly showed the negative shift of the L-type Ca 2+ current (I CaL ) takeoff potential, enlargement of the sustained inward current (I st ), and the hyperpolarization-activated nonselective cation current (I ha ) played major roles in increasing the firing frequency. Deactivation of I Ks during diastole scarcely contributed to the time-dependent decrease in membrane K + conductance, which was the major mechanism for slow diastolic depolarization, as indicated by calculating the instantaneous equilibrium potential (lead potential). This was because the activation of I Ks during the preceding action potential was negligibly small. However, I Ks was important in counterbalancing the increase in I CaL and the Na + /Ca 2+ exchange current (I NaCa ), which otherwise compromised the positive chronotropic effect by elongating the action potential duration. Enhanced Ca 2+ release from the sarcoplasmic reticulum failed to induce an obvious chronotropic effect in our model.Key words: β1-adrenergic receptor, cardiac pacemaker model, sinoatrial node, sympathetic nerve stimulation, simulation.Sympathetic stimulation of SA node pacemaker cells (SANs) is essential for increasing heart rate when a larger blood supply is required for the body. The autonomic neurotransmitter, noradrenaline, is released from nerve terminals, binds to the β1-adrenergic receptor, and initiates intracellular signal transduction in SANs, which causes the increased firing frequency of spontaneous action potentials. This positive chronotropy is due to a variety of functional modifications of ion channels and ion transporters. To date, electrophysiological and pharmacological studies have provided experimental evidence to show that ion channels and transporters are modified by the β1-adrenergic stimulation. To clarify the contributions of each current, however, an integrative analysis is required because positive chronotropy is induced by multiple interactions of all ion channels and transporters, which have different kinetics and respond differently to β1-adrenergic stimulation. In 2003, we developed a SAN model that included spontaneous action potential generation and intracellular ion homeostasis, including Ca 2+ dynamics [1,2]. Using this model, we proposed the principal ionic mechanisms underlying the spontaneous action potential. In the...

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Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking Na+/K+ Pump As Revealed by Experiments and Simulation

Cited by 64 publications

References 70 publications

Physiology of Cell Volume Regulation in Vertebrates

Physiology of Cell Volume Regulation in Vertebrates

Age-Dependent Brain Tissue Hydration, Ca Exchange and their Dose- Dependent Ouabain Sensitivity

Ionic Mechanisms Underlying the Positive Chronotropy Induced by β1-Adrenergic Stimulation in Guinea Pig Sinoatrial Node Cells: a Simulation Study

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