Rosana Almada Bassani

@article{Milan2023,

title = {Membrane polarization at the excitation threshold induced by external electric fields in cardiomyocytes of rats at different developmental stages},

author = {Hugo F. M. Milan and Ahmad A. Almazloum and Rosana A Bassani and José W M Bassani},

doi = {10.1007/s11517-023-02868-1},

issn = {1741-0444},

year  = {2023},

date = {2023-10-00},

urldate = {2023-10-00},

journal = {Med Biol Eng Comput},

volume = {61},

number = {10},

pages = {2637--2647},

publisher = {Springer Science and Business Media LLC},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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{pmid33556894,

title = {The ForceLAB simulator: Application to the comparison of current models of cardiomyocyte contraction},

author = {Robson Rodrigues da Silva and Osias Baptista de Souza Filho and José Wilson Magalhães Bassani and Rosana Almada Bassani},

doi = {10.1016/j.compbiomed.2021.104240},

issn = {1879-0534},

year  = {2021},

date = {2021-04-01},

journal = {Comput Biol Med},

volume = {131},

pages = {104240},

abstract = {Mathematical models are useful tools in the study of physiological phenomena. However, due to differences in assumptions and formulations, discrepancy in simulations may occur. Among the models for cardiomyocyte contraction based on Huxley's cross-bridge cycling, those proposed by Negroni and Lascano (NL) and Rice et al. (RWH) are the most frequently used. This study was aimed at developing a computational tool, ForceLAB, which allows implementing different contraction models and modifying several functional parameters. As an application, electrically-stimulated twitches triggered by an equal Ca input and steady-state force x pCa relationship (pCa = -log of the molar free Ca concentration) simulated with the NL and RWH models were compared. The equilibrium Ca-troponin C (TnC) dissociation constant (K) was modified by changing either the association (k) or the dissociation (k) rate constant. With the NL model, raising K by either maneuver decreased monotonically twitch amplitude and duration, as expected. With the RWH model, in contrast, the same K variation caused increase or decrease of peak force depending on which rate constant was modified. Additionally, force x pCa curves simulated using Ca binding constants estimated in cardiomyocytes bearing wild-type and mutated TnC were compared to curves previously determined in permeabilized fibers. Mutations increased k and k, and decreased K. Both models produced curves fairly comparable to the experimental ones, although sensitivity to Ca was greater, especially with RWH model. The NL model reproduced slightly better the qualitative changes associated with the mutations. It is expected that this tool can be useful for teaching and investigation.},

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{pmid31667705,

title = {Accuracy of electromagnetic models to estimate cardiomyocyte membrane polarization},

author = {Hugo F M Milan and Rosana Almada Bassani and Luiz E C Santos and Antonio C G Almeida and José Wilson Magalhães Bassani},

doi = {10.1007/s11517-019-02054-2},

issn = {1741-0444},

year  = {2019},

date = {2019-12-01},

urldate = {2019-12-01},

journal = {Med Biol Eng Comput},

volume = {57},

number = {12},

pages = {2617--2627},

abstract = {External electric fields (E) induce a spatially heterogeneous variation in the membrane potential (ΔV) of cardiomyocytes that, if sufficiently large, results in an action potential and contraction. Insights into the phenomenon of ΔV induction by E have been classically gained with electromagnetic models due to the lack of adequate experimental approaches. However, it is not clear yet how reliable these models are. To assess the accuracy of commonly used models, a reference 3D numerical model for cardiomyocytes (NMReal) was developed, consisting of the cell membrane shell reconstructed from rendered confocal microscopy images of freshly isolated ventricular myocytes. NMReal was used to estimate the E-induced maximum ΔV values (ΔV), which were compared with estimates from seven other electromagnetic models. Accurate ΔV estimates (average error < 2%) were obtained with a less complex 3D model (NM3D) based on the extruded 2D image of the cell longitudinal section. Acceptable ΔV estimates (average error < 5%) were obtained with the prolate spheroid analytical model (PSAM) when the angle of E incidence and the cell major axis was < 30°. In this case, PSAM, a much simpler model requiring only the measurement of the longitudinal and transversal cell dimensions, can be a suitable alternative for ΔV calculation. Graphical abstract (A) Confocal images of the cell were used to reconstruct the realistic geometry of cardiomyocytes (NMReal). (B) NMReal was used to estimate the maximum variation in the transmembrane potential (ΔV) induced by an external electric field (E) applied at different angles with respect to the cell major axis. Plus (anode) and minus (cathode) signs indicate electrode position (E direction is from minus to plus). (C) Relative error (vs. NMReal) of ΔV estimation with simplified electromagnetic models, presented in descending order of accuracy (left-to-right, top-to-bottom). NM2D: 2D numerical model based on the longitudinal cell image; NM3D: numerical model based on the z extrusion of NM2D; EAM, PSAM, and CAM: ellipsoidal, prolate spheroidal, and cylindrical analytical models, respectively; PNM and CNM: parallelepipedal and cylindrical numerical models, respectively.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}