Pulsed electric fields with high intensity (MV/m) and duration in the sub-?s to- ns time scale (nsPEFs) are known to increase the permeability of biological membranes, and to induce morphological and functional alterations of the physiological status of the cell, including swelling , caspase activation and apoptosis and release of intracellular calcium. Recent papers have also demonstrated that nsPEFs might be used to induce stimulation and/or inhibition of excitable cells and tissues, with possible applications for neuro-stimulation or defibrillation. Such phenomena have been observed in in vitro and ex vivo studies, but the basic interactions mechanisms between nsPEFs and the complex structure of mammalian cell membranes still need to be elucidated. A modelistic approach can be very helpful to this aim, in order to predict phenomena occurring on temporal and/or spatial scales that are not experimentally accessible. In our previous paper (Lamberti et al, IEEE Transactions on Nanobioscience, 17 (2), 110-116, 2018), the circuital model of the plasma membrane of a giant squid axon was developed by means of the PSIM (Power Simulator, Powersim Inc., Rockville, MD, USA) environment, a power electronics simulation tool. The Hodgkin and Huxley (HH) set of equations, describing onset of action potentials (AP), were implemented. More specifically, the initial depolarization is provided in our model as an ideal current density pulse, with assigned duration and amplitude, whose value is set according to the charge accumulated across the membrane capacitance The model was first validated under the stimulation conditions of the HH experiments, i.e. single, 200 ?s long stimuli and initial depolarization of 6,7,15, and 90 mV. The physiological responses recorded in the HH experiments were successfully reproduced under liminal, subliminal and supraliminal stimulation conditions. Moreover, the model was challenged by analysing excitation conditions under 1, 10 and 100 ns long pulses. The results demonstrated the possibility of electrostimulation by nsPEFs at depolarization levels far below those required for inducing electroporation, In this contribution, the dynamics of ionic channels currents under nsPEFs stimulation will be presented and compared to that of conventional pulses. These results confirm recent experimental evidence that nsPEFs can stimulate peripheral nerves with direct activation of voltage-gated channels, in absence of electroporation injury.
Dynamics of ionic channel currents in a circuital, Hodgkin-Huxley model of an axon under ns pulsed electric field stimulation
Stefania Romeo
2019
Abstract
Pulsed electric fields with high intensity (MV/m) and duration in the sub-?s to- ns time scale (nsPEFs) are known to increase the permeability of biological membranes, and to induce morphological and functional alterations of the physiological status of the cell, including swelling , caspase activation and apoptosis and release of intracellular calcium. Recent papers have also demonstrated that nsPEFs might be used to induce stimulation and/or inhibition of excitable cells and tissues, with possible applications for neuro-stimulation or defibrillation. Such phenomena have been observed in in vitro and ex vivo studies, but the basic interactions mechanisms between nsPEFs and the complex structure of mammalian cell membranes still need to be elucidated. A modelistic approach can be very helpful to this aim, in order to predict phenomena occurring on temporal and/or spatial scales that are not experimentally accessible. In our previous paper (Lamberti et al, IEEE Transactions on Nanobioscience, 17 (2), 110-116, 2018), the circuital model of the plasma membrane of a giant squid axon was developed by means of the PSIM (Power Simulator, Powersim Inc., Rockville, MD, USA) environment, a power electronics simulation tool. The Hodgkin and Huxley (HH) set of equations, describing onset of action potentials (AP), were implemented. More specifically, the initial depolarization is provided in our model as an ideal current density pulse, with assigned duration and amplitude, whose value is set according to the charge accumulated across the membrane capacitance The model was first validated under the stimulation conditions of the HH experiments, i.e. single, 200 ?s long stimuli and initial depolarization of 6,7,15, and 90 mV. The physiological responses recorded in the HH experiments were successfully reproduced under liminal, subliminal and supraliminal stimulation conditions. Moreover, the model was challenged by analysing excitation conditions under 1, 10 and 100 ns long pulses. The results demonstrated the possibility of electrostimulation by nsPEFs at depolarization levels far below those required for inducing electroporation, In this contribution, the dynamics of ionic channels currents under nsPEFs stimulation will be presented and compared to that of conventional pulses. These results confirm recent experimental evidence that nsPEFs can stimulate peripheral nerves with direct activation of voltage-gated channels, in absence of electroporation injury.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
