Natália Ferreira Oshiyama

@article{pmid35489088,

title = {Developmental differences in myocardial transmembrane Na transport: implications for excitability and Na handling},

author = {Natália Ferreira Oshiyama and Ana H M Pereira and Alisson C Cardoso and Kleber G Franchini and José Wilson Magalhães Bassani and Rosana Almada Bassani},

doi = {10.1113/JP282661},

issn = {1469-7793},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {J Physiol},

volume = {600},

number = {11},

pages = {2651--2667},

abstract = {Little is currently known about possible developmental changes in myocardial Na handling, which may have impact on cell excitability and Ca content. Resting intracellular Na concentration ([Na ] ), measured in freshly isolated rat ventricular myocytes with CoroNa green, was not significantly different in neonates (3-5 days old) and adults, but electrical stimulation caused marked [Na ] rise only in neonates. Inhibition of L-type Ca current by CdCl abolished not only systolic Ca transients, but also activity-dependent intracellular Na accumulation in immature cells. This indicates that the main Na influx pathway during activity is the Na /Ca exchanger, rather than voltage-dependent Na current (I ), which was not affected by CdCl . In immature myocytes, I density was two-fold greater, inactivation was faster, and the current peak occurred at less negative transmembrane potential (E ) than in adults. Na channel steady-state activation and inactivation curves in neonates showed a rightward shift, which should increase channel availability at diastolic E , but also require greater depolarization for excitation, which was observed experimentally and reproduced in computer simulations. Ventricular mRNA levels of Na 1.1, Na 1.4 and Na 1.5 pore-forming isoforms were greater in neonate ventricles, while a decrease was seen for the β1 subunit. Both molecular and biophysical changes in the channel profile may contribute to the differences in I density and voltage-dependence, and also to the less negative threshold E , in neonates compared to adults. The apparently lower excitability in immature ventricle may confer protection against the development of spontaneous activity in this tissue. KEY POINTS: Previous studies showed that myocardial preparations from immature rats are less sensitive to electrical field stimulation than adult preparations. Freshly isolated ventricular myocytes from neonatal rats showed lower excitability than adult cells, e.g. less negative threshold membrane potential and greater membrane depolarization required for action potential triggering. In addition to differences in mRNA levels for Na channel isoforms and greater Na current (I ) density, Na channel voltage-dependence was shifted to the right in immature myocytes, which seems to be sufficient to decrease excitability, according to computer simulations. Only in neonatal myocytes did cyclic activity promote marked cytosolic Na accumulation, which was prevented by abolition of systolic Ca transients by blockade of Ca currents. Developmental changes in I may account for the difference in action potential initiation parameters, but not for cytosolic Na accumulation, which seems to be due mainly to Na /Ca exchanger-mediated Na influx.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Impact of voltage-gated Na + channel biophysical properties on action potential upstroke},

author = {Natália Ferreira Oshiyama and Rosana Almada Bassani and José Wilson Magalhães Bassani},

doi = {https://doi.org/10.1016/j.yjmcc.2019.11.116},

year  = {2020},

date = {2020-03-01},

urldate = {2020-03-01},

journal = {Journal of Molecular and Cellular Cardiology},

volume = {140},

pages = {48-49},

abstract = {The main determinant of conduction velocity is the AP maximum depolarization rate (dEm/dtmax), which depends on the voltage-gated Na+ channels biophysical properties. Here we investigated age-dependent differences in whole-cell Na+ current (INa) and dEm/dtmax in myocytes isolated from neonatal and adult Wistar rats. The impact of Na+ channel biophysical properties on AP overshoot was evaluated with an AP model developed with measured whole-cell INa, Ca2+, and transient outward and delayed rectifier K+ currents from immature cells, described according to Hodgkin-Huxley kinetics. Even though INa density was 2-fold greater in neonatal myocytes (−71.9 ± 35.5, n = 11; 33.3 ± 1 6.7 pA/pF in adults, n = 6; p < .01), dEm/dtmax was not, and tended to be lower in neonates (84.2 ± 35.8 V/s, n = 12) than in adults (100.3 ± 44.4 V/s, n = 7; p = .40). The half-maximal activation voltage (E1/2) was less negative (−31.5 ± 1.7 mV vs. -44.4 ± 6.0 mV; p < .001), and the activation curve had greater slope (k: 7.8 ± 1.2 mV vs. 4.4 ± 0.6 mV; p < .001) in immature than in adult cells. A positive shift was also observed in the steady-state inactivation curve in neonates (E1/2: −76.2 ± 7.8 mV vs. -85.6 ± 4.1 mV; p < .05). The dEm/dtmax of the simulated AP in neonatal myocyte was 81 V/s. However, when the activation and inactivation equations were adjusted to reproduce E1/2 and k values estimated in adult cells, dEm/dtmax increased to 96 V/s, close to the experimental value in adults. Therefore, it seems that, in addition to INa density, voltage-dependence of Na+ channel activation and inactivation may exert marked influence on depolarization rate, and AP propagation velocity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Impact of voltage-gated Na + channel biophysical properties on action potential upstroke},

author = {Natália Ferreira Oshiyama and Rosana Almada Bassani and José Wilson Magalhães Bassani},

doi = {https://doi.org/10.1016/j.yjmcc.2019.11.116},

year  = {2020},

date = {2020-03-01},

volume = {140},

pages = {48-49},

abstract = {The main determinant of conduction velocity is the AP maximum depolarization rate (dEm/dtmax), which depends on the voltage-gated Na+ channels biophysical properties. Here we investigated age-dependent differences in whole-cell Na+ current (INa) and dEm/dtmax in myocytes isolated from neonatal and adult Wistar rats. The impact of Na+ channel biophysical properties on AP overshoot was evaluated with an AP model developed with measured whole-cell INa, Ca2+, and transient outward and delayed rectifier K+ currents from immature cells, described according to Hodgkin-Huxley kinetics. Even though INa density was 2-fold greater in neonatal myocytes (−71.9 ± 35.5, n = 11; 33.3 ± 1 6.7 pA/pF in adults, n = 6; p < .01), dEm/dtmax was not, and tended to be lower in neonates (84.2 ± 35.8 V/s, n = 12) than in adults (100.3 ± 44.4 V/s, n = 7; p = .40). The half-maximal activation voltage (E1/2) was less negative (−31.5 ± 1.7 mV vs. -44.4 ± 6.0 mV; p < .001), and the activation curve had greater slope (k: 7.8 ± 1.2 mV vs. 4.4 ± 0.6 mV; p < .001) in immature than in adult cells. A positive shift was also observed in the steady-state inactivation curve in neonates (E1/2: −76.2 ± 7.8 mV vs. -85.6 ± 4.1 mV; p < .05). The dEm/dtmax of the simulated AP in neonatal myocyte was 81 V/s. However, when the activation and inactivation equations were adjusted to reproduce E1/2 and k values estimated in adult cells, dEm/dtmax increased to 96 V/s, close to the experimental value in adults. Therefore, it seems that, in addition to INa density, voltage-dependence of Na+ channel activation and inactivation may exert marked influence on depolarization rate, and AP propagation velocity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31084419,

title = {High Thyrotropin Is Critical for Cardiac Electrical Remodeling and Arrhythmia Vulnerability in Hypothyroidism},

author = {Julieta Fernandez-Ruocco and Monica Gallego and Ainhoa Rodriguez-de-Yurre and Julian Zayas-Arrabal and Leyre Echeazarra and Amaia Alquiza and Victor Fernández-López and Juan M Rodriguez-Robledo and Oscar Brito and Ygor Schleier and Marisa Sepulveda and Natália Ferreira Oshiyama and Martin Vila-Petroff and Rosana Almada Bassani and Emiliano H Medei and Oscar Casis},

doi = {10.1089/thy.2018.0709},

issn = {1557-9077},

year  = {2019},

date = {2019-07-01},

urldate = {2019-07-01},

journal = {Thyroid},

volume = {29},

number = {7},

pages = {934--945},

abstract = { Hypothyroidism, the most common endocrine disease, induces cardiac electrical remodeling that creates a substrate for ventricular arrhythmias. Recent studies report that high thyrotropin (TSH) levels are related to cardiac electrical abnormalities and increased mortality rates. The aim of the present work was to investigate the direct effects of TSH on the heart and its possible causative role in the increased incidence of arrhythmia in hypothyroidism.  A new rat model of central hypothyroidism (low TSH levels) was created and characterized together with the classical propylthiouracil-induced primary hypothyroidism model (high TSH levels). Electrocardiograms were recorded , and ionic currents were recorded from isolated ventricular myocytes  by the patch-clamp technique. Protein and mRNA were measured by Western blot and quantitative reverse transcription polymerase chain reaction in rat and human cardiac myocytes. Adult human action potentials were simulated  to incorporate the experimentally observed changes.  Both primary and central hypothyroidism models increased the L-type Ca current (I) and decreased the ultra-rapid delayed rectifier K current (I) densities. However, only primary but not central hypothyroidism showed electrocardiographic repolarization abnormalities and increased ventricular arrhythmia incidence during caffeine/dobutamine challenge. These changes were paralleled by a decrease in the density of the transient outward K current (I) in cardiomyocytes from animals with primary but not central hypothyroidism.  treatment with TSH for 24 hours enhanced isoproterenol-induced spontaneous activity in control ventricular cells and diminished I density in cardiomyocytes from control and central but not primary hypothyroidism animals. In human myocytes, TSH decreased the expression of  and , I, and the delayed rectifier K current (I) encoding proteins in a protein kinase A-dependent way. Transposing the changes produced by hypothyroidism and TSH to a computer model of human ventricular action potential resulted in enhanced occurrence of early afterdepolarizations and arrhythmia mostly in primary hypothyroidism, especially under β-adrenergic stimulation.  The results suggest that suppression of repolarizing K currents by TSH underlies most of the electrical remodeling observed in hypothyroidism. This work demonstrates that the activation of the TSH-receptor/protein kinase A pathway in the heart is responsible for the cardiac electrical remodeling and arrhythmia generation seen in hypothyroidism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Medical equipment classification according to corrective maintenance data: a strategy based on the equipment age},

author = {Natália Ferreira Oshiyama and Ana Carolina Silveira and Rosana Almada Bassani and José Wilson Magalhães Bassani},

doi = {https://doi.org/10.4322/rbeb.2013.045},

year  = {2014},

date = {2014-04-23},

journal = {Rev. Bras. Eng. Bioméd},

volume = {30},

issue = {1},

abstract = {Decision-making on medical equipment management is a daily task for clinical engineers, but it may prove difficult to easily extract relevant information from the large amount of data from computerized maintenance management systems. This article describes a simple method of medical equipment classification based on corrective maintenance indicators. METHODS: Three indicators were calculated based on the number of events, duration and cost of corrective maintenance. Three classes were defined according to the indicator values of different equipment ages: class A for 0-4 years, class B for 5-9 years, and class C for equipment older than 10 years. The method was applied to 2,134 pieces of equipment from the Health Service system of the University of Campinas. RESULTS: From the total, 51.7% of the equipment were classified as C, 4.2% as B and 44.1% as A. The infusion pump for general use was the type of equipment of which most units were in the C class (84.7%), even though almost 50% of them were acquired within less than 9 years, and would thus be expected to be classified as A and B. Among the pumps in class C, 39.5% were from a single manufacturer, although the equipments were acquired recently. CONCLUSION: The developed classification may be an important tool for raising alerts about equipment more prone to maintenance problems, as well as for identification of equipments with acceptable maintenance history, supporting decision-making on equipment replacement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24140800,

title = {Muscarinic stimulation and pinacidil produce similar facilitation of tachyarrhythmia induction in rat isolated atria},

author = {Nivaldo Zafalon and Natália Ferreira Oshiyama and José Wilson Magalhães Bassani and Rosana Almada Bassani},

doi = {10.1016/j.yjmcc.2013.10.004},

issn = {1095-8584},

year  = {2013},

date = {2013-12-01},

urldate = {2013-12-01},

journal = {J Mol Cell Cardiol},

volume = {65},

pages = {120--126},

abstract = {Atrial tachyarrhythmias, the most common type of cardiac arrhythmias, are associated with greater stroke risk. Muscarinic cholinergic agonists have been shown to facilitate atrial tachyarrhythmia maintenance in the absence of cardiac disease. This has been attributed to action potential shortening, which enhances myocardial electrical anisotropy, and thus creates a substrate for reentrant excitation. In this study, we describe a similar effect of the ATP-sensitive K(+) channel (KATP) opener pinacidil on tachyarrhythmia induction in isolated rat atria. Pinacidil, which activates a weakly inwardly-rectifying current in isolated atrial myocytes, enhanced arrhythmia induction in the right and left atria. This effect was abolished by the KATP blocker glibenclamide, but not by atropine, which rules out a possible indirect effect due to stimulation of acetylcholine release. However, pinacidil attenuated carbachol-induced tachyarrhythmia facilitation, which may indicate that the action of these agonists converges to a common cellular mechanism. Both agonists caused marked action potential shortening in isolated atrial myocytes. Moreover, during arrhythmia in the presence of pinacidil and carbachol, the atrial vectorelectrographic patterns were similar and consistent with reentrant propagation of the electrical activity. From these results, we conclude that the KATP channel opening is pro-arrhythmic in atrial tissue, which may pose as an additional risk in the scenario of myocardial hypoxia. Moreover, the similarity of the electrophysiological effects of pinacidil and carbachol is suggestive that the sole increase in background K(+) conductance is sufficient for atrial tachyarrhythmia facilitation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}