Analysis of electric field stimulation of single cardiac muscle cells.

Electrical stimulation of cardiac cells by imposed extracellular electric fields results in a transmembrane potential which is highly nonuniform, with one end of the cell depolarized and the other end hyperpolarized along the field direction. To date, the implications of the close proximity of oppositely polarized membranes on excitability have not been explored. In this work we compare the biophysical basis for field stimulation of cells at rest with that for intracellular current injection, using three Luo-Rudy type membrane patches coupled together as a lumped model to represent the cell membrane. Our model shows that cell excitation is a function of the temporal and spatial distribution of ionic currents and transmembrane potential. The extracellular and intracellular forms of stimulation were compared in greater detail for monophasic and symmetric biphasic rectangular pulses, with duration ranging from 0.5 to 10 ms. Strength-duration curves derived for field stimulation show that over a wide range of pulse durations, biphasic waveforms can recruit and activate membrane patches about as effectively as can monophasic waveforms having the same total pulse duration. We find that excitation with biphasic stimulation results from a synergistic, temporal summation of inward currents through the sodium channel in membrane patches at opposite ends of the cell. Furthermore, with both waveform types, a net inward current through the inwardly rectifying potassium channel contributes to initial membrane depolarization. In contrast, models of stimulation by intracellular current injection do not account for the nonuniformity of transmembrane potential and produce substantially different (even contradictory) results for the case of stimulation from rest.     

Paradoxical loss of excitation with high intensity pulses during electric field stimulation of single cardiac cells

Transmembrane potential responses of single cardiac cells stimulated at rest were studied with uniform rectangular field pulses having durations of 0.5-10 ms. Cells were enzymatically isolated from guinea pig ventricles, stained with voltage sensitive dye di-8-ANEPPS, and stimulated along their long axes. Fluorescence signals were recorded with spatial resolution of 17 microm for up to 11 sites along the cell. With 5 and 10 ms pulses, all cells (n = 10) fired an action potential over a broad range of field amplitudes (approximately 3-65 V/cm). With 0.5 and 1 ms pulses, all cells (n = 7) fired an action potential for field amplitudes ranging from the threshold value (approximately 4-8 V/cm) to 50-60 V/cm. However, when the field amplitude was further increased, five of seven cells failed to fire an action potential. We postulated that this paradoxical loss of excitation for higher amplitude field pulses is the result of nonuniform polarization of the cell membrane under conditions of electric field stimulation, and a counterbalancing interplay between sodium current and inwardly rectifying potassium current with increasing field strength. This hypothesis was verified using computer simulations of a field-stimulated guinea pig ventricular cell. In conclusion, we show that for stimulation with short-duration pulses, cells can be excited for fields ranging between a low amplitude excitation threshold and a high amplitude threshold above which the excitation is suppressed. These results can have implications for the mechanistic understanding of defibrillation outcome, especially in the setting of diseased myocardium.     

Unpinning of a rotating wave in cardiac muscle by an electric field.

The possibility of terminating cardiac arrhythmias with electric fields of moderate intensity is a challenging problem from a fundamental point of view and an important issue for clinical applications. In an effort to understand how anatomical re-entries are affected by electric fields, we found that a weak shock, with an amplitude of an order of magnitude less than the defibrillating shock, may unpin the vortices rotating around the defects (obstacles). The unpinning results from a depolarization of the tissue near the obstacle, induced by an external electric field within a distance of order lambda approximately 1 mm. Unpinning was observed both in the FitzHugh model of excitable tissue, and in a specific Beeler-Reuter model of cardiac tissue. This theoretical observation suggests that anatomical re-entries can be transformed into functional re-entries, an effect that can be tested in experiments with cardiac muscle.     

Physiological stimulation of plants using delayed and regulated electric field environments

Electric field conditions have been regulated for optimum growth of corn as determined from field delay experiments on both corn and bean plants in a reversed electrostatic field, a conventional electrostatic field,and an electrokinetic (60 cps) field. These experiments have established the critical dynamic potential gradient (field strength necessary to induce physical leaf damage)at about 100 kv/m for extended electrification ( >10 hr) or corn and bean plants.Field delay or field intensity-time duration experiments on corn and bean plants allow a possible relationship between plant growth and storm conditions in the natural environment to be established.

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Zusammenfassung Es wurden elektrische Feldbedingungen für optimales Wachstum von Mais eingestellt, die in Feldverzögerungs-Experimenten mit Mais- und Bohnenpflanzen im umgekehrten elektrostatischen Feld, konventionellen elektrostatischen und elektrokinetischen (60 cps) Feld ausgearbeitet worden waren. Uber diese Experimente wurde der kritische dynamische Potentialgradient für Mais- und Bohnenpflanzen erarbeitet, das ist die Feldstärke, die erforderlich ist,um wirklichen Blattschaden zu erzeugen. Er liegt bei ausgedehnter Elektrifizierung ( >10 hr)bei ungefähr 100 kv/m. Feldverzögerungs- oder Feldintensitäts-Dauerexperimente mit Mais- und Bohnenpflanzen gestatten die Ausarbeitung der möglichen Beziehungen zwischen Pflanzenwachstum und Gewitter in der natürlichen Umwelt.

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Resume On a établi des conditions de champ électriques provoquant une croissance optimum du maïs. Pour ce faire, on s'est basé sur des recherches portant sur les effets de retardement dû au champ tant sur le maïs que sur des pois dans un champ êlectrostatique renversé, conventionnel ou électro-cinétique (60 imp/sec). Ces essais ont permis d'établir un gradient potentiel dynamique critique (champ absolument indispensable pour occasionner des dégâts physiques aux feuilles)et cela pour les deux dites plantes. Ce gradient est voisin de 100 kv/m pour une mise sous tension de longue durée (plus de 10 heures). Des essais de durée de l'intensité du champ ou de son effet retardateur, essais effectués sur du maïs et sur des pois,permettent détablir la relation probable qui existe entre la croissance des plantes et les conditions orageuses naturelles.

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Presented during the Fourth Int.Biometeor.Congress, New Brunswick, N.J., 26 August – 2 September 1966.     

The cardiac electric field in psychrophilic and thermophilic fish during atrial depolarization

In psychrophilic and thermophilic fish, significant differences were revealed under an optimal body temperature in the heart rate, initial atrial activity duration and descending slope of the P _II wave. Differences were also detected in atrial electric activity during the initial and final periods of depolarization, reflecting different localization of the initial excitation area and the movement of the depolarization front toward the atrioventricular border.     

外加电场刺激对菲降解菌的影响

以菲为主要C源,吐温80作为增溶剂,研究细菌Enterobacter dissolvens在直流电和交流电条件下的生长和代谢过程。实验结果表明:当施加10 mA直流电时,通电8 h后,菌液中细胞的菲降解率较对照增长1.6倍,细胞生长亦有所加快;而施加交流电时,细菌生长和菲降解率均低于直流电刺激。     

Destabilization of the cardiac function of an insect by a low-frequency electric field

The effect of high-intensity low-frequency electric field on the functioning of the heart of an insect was estimated from electrocardiogram. It was found that electric field causes a disturbance of the cardiac function. Its stressing activity is mainly related to the excitation of the insect by induced currents whose exciting action is enhanced by vibration in trichoid sensillas and antennas.     

Synchronization of neuron population subject to steady DC electric field induced by magnetic stimulation

Electric fields, which are ubiquitous in the context of neurons, are induced either by external electromagnetic fields or by endogenous electric activities. Clinical evidences point out that magnetic stimulation can induce an electric field that modulates rhythmic activity of special brain tissue, which are associated with most brain functions, including normal and pathological physiological mechanisms. Recently, the studies about the relationship between clinical treatment for psychiatric disorders and magnetic stimulation have been investigated extensively. However, further development of these techniques is limited due to the lack of understanding of the underlying mechanisms supporting the interaction between the electric field induced by magnetic stimulus and brain tissue. In this paper, the effects of steady DC electric field induced by magnetic stimulation on the coherence of an interneuronal network are investigated. Different behaviors have been observed in the network with different topologies (i.e., random and small-world network, modular network). It is found that the coherence displays a peak or a plateau when the induced electric field varies between the parameter range we defined. The coherence of the neuronal systems depends extensively on the network structure and parameters. All these parameters play a key role in determining the range for the induced electric field to synchronize network activities. The presented results could have important implications for the scientific theoretical studies regarding the effects of magnetic stimulation on human brain.     

New electric field methods in chemical relaxation spectrometry.

New stationary relaxation methods for the investigation of ionic and dipolar equilibria are presented. The methods are based on the measurement of non-linearities in conductance and permittivity under high electric field conditions. The chemical contributions to the nonlinear effects are discussed in their static as well as their dynamic behavior. A sampling of experimental results shows the potential and range of possible applications of the new techniques. It is shown that these methods will become useful in the study of nonlinear responses to perturbation, in view of the general applicability of the experimental principles involved.     

Remodeling of cardiac fiber structure after infarction in rats quantified with diffusion tensor MRI

Structural remodeling of myocardium after infarction plays a critical role in functional adaptation. Diffusion tensor magnetic resonance imaging (DTMRI) provides a means for rapid and nondestructive characterization of the three-dimensional fiber architecture of cardiac tissues. In this study, microscopic structural changes caused by MI were evaluated in Fischer 344 rats 4 wk after infarct surgery. DTMRI studies were performed on 15 excised, formalin-fixed rat hearts of both infarct (left anterior descending coronary artery occlusion, n = 8) and control (sham, n = 7) rats. Infarct myocardium exhibited increased water diffusivity (41% increase in trace values) and decreased diffusion anisotropy (37% decrease in relative anisotropy index). The reduced diffusion anisotropy correlated negatively with microscopic fiber disarray determined by histological analysis (R = 0.81). Transmural courses of fiber orientation angles in infarct zones were similar to those of normal myocardium. However, regional angular deviation of the diffusion tensor increased significantly in the infarct myocardium and correlated strongly with microscopic fiber disarray (R = 0.86). These results suggest that DTMRI may provide a valuable tool for defining structural remodeling in diseased myocardium at the cellular and tissue level.     

Phase resetting in a model of cardiac Purkinje fiber.

The phase-resetting response of a model of spontaneously active cardiac Purkinje fiber is investigated. The effect on the interbeat interval of injecting a 20-ms duration depolarizing current pulse is studied as a function of the phase in the cycle at which the pulse is delivered. At low current amplitudes, a triphasic response is recorded as the pulse is advanced through the cycle. At intermediate current amplitudes, the response becomes quinquephasic, due to the presence of supernormal excitability. At high current amplitudes, a triphasic response is seen once more. At low stimulus amplitudes, type 1 phase resetting occurs; at medium amplitudes, a type could not be ascribed to the phase resetting because of the presence of effectively all-or-none depolarization; at high amplitudes, type 0 phase resetting occurs. The modeling results closely correspond with published experimental data; in particular type 1 and type 0 phase resetting are seen. Implications for the induction of ventricular arrhythmias are considered.     

Effect of electric field on erythrocyte sedimentation rate. II. Dependence on electric current

We measured the electric current dependence of sedimentation curves of swine erythrocytes in a saline solution at the volume fraction of erythrocytes H = 0.091 and 0.220. The sedimentation curve fitted well to the exponential type equation l = a[1-exp(-bt)] at the upward initial electric current I0 = 0.50 mA, 1.01 mA and 1.50 mA, where l is the length of the medium layer at time t, and a and b are phenomenological parameters. The initial slope v0 of sedimentation curve was enhanced from 0.68 mm/hr at I0 = 0 mA to 2.85 mm/hr, 3.87 mm/hr and 5.50 mm/hr at I0 = 0.50 mA, 1.01 mA and 1.50 mA, respectively, for H = 0.220. We also made sedimentation measurements of erythrocytes in their own plasma at H = 0.220 and 0.316. Sedimentation curves coincided with the sigmoidal type equation l = l infinity/[1 + (t50/t)beta] at I0 = 0 mA and 0.50 mA, where l infinity is l at t----infinity, t50 is the time when the plasma level falls to l infinity/2 and beta is a constant. The maximum slope vmax of sedimentation curve increased from 13.29 mm/hr at I0 = 0 mA to 18.65 mm/hr at I0 = 0.50 mA for H = 0.220.     

Influence of the electric field on supramolecular structure and properties of amyloid-specific reagent Congo red

Among specific amyloid ligands, Congo red and its analogues are often considered potential therapeutic compounds. However, the results of the studies so far have not been univocal because the properties of this dye, derived mostly from its supramolecular nature, are still poorly understood. The supramolecular structure of Congo red, formed by π-π stacking of dye molecules, is susceptible to the influence of the electric field, which may significantly facilitate electron delocalization. Consequently, the electric field may generate altered physico-chemical properties of the dye. Enhanced electron delocalization, induced by the electric field, alters the total charge of Congo red, making the dye more acidic (negatively charged). This is a consequence of withdrawing electrons from polar substituents of aromatic rings-sulfonic and amino groups-thus increasing their tendency to dissociate protons. The electric field-induced charge alteration observed in electrophoresis depends on dye concentration. This concentration-dependent charge alteration effect disappears when the supramolecular structure disintegrates in DMSO. Dipoles formed from supramolecular fibrillar species in the electric field become ordered in the solution, introducing the modified arrangement to liquid crystalline phase. Experimental results and theoretical studies provide evidence confirming predictions that the supramolecular character of Congo red is the main reason for its specific properties and reactivity.     

Myosin types and fiber types in cardiac muscle. I. Ventricular myocardium

Antisera against bovine atrial myosin were raised in rabbits, purified by affinity chromatography, and absorbed with insolubilized ventricular myosin. Specific anti-bovine atrial myosin (anti-bAm) antibodies reacted selectively with atrial myosin heavy chains, as determined by enzyme immunoassay combined with SDS-gel electrophoresis. In direct and indirect immunofluorescence assay, anti-bAm was found to stain all atrial muscle fibers and a minor proportion of ventricular muscle fibers in the right ventricle of the bovine heart. In contrast, almost all muscle fibers in the left ventricle were unreactive. Purkinje fibers showed variable reactivity. In the rabbit heart, all atrial muscle fibers were stained by anti-bAm, whereas ventricular fibers showed a variable response in both the right and left ventricle, with a tendency for reactive fibers to be more numerous in the right ventricle and in subepicardial regions. Diversification of fiber types with respect to anti-bAm reactivity was found to occur during late stages of postnatal development in the rabbit heart and to be influenced by thyroid hormone. All ventricular muscle fibers became strongly reactive after thyroxine treatment, whereas they became unreactive or poorly reactive after propylthiouracil treatment. These findings are consistent with the existence of different ventricular isomyosins whose relative proportions can vary according to the thyroid state. Variations in ventricular isomyosin composition can account for the changes in myosin Ca2+-activated ATPase activity previously observed in cardiac muscle from hyper- and hypothyroid animals and may be responsible for the changes in the velocity of contraction of ventricular myocardium that occur under these conditions. The differential distribution of ventricular isomyosins in the normal heart suggests that fiber types with different contractile properties may coexist in the ventricular myocardium.     

Myosin types and fiber types in cardiac muscle. II. Atrial myocardium

Antibodies were produced against myosins isolated from the left atrial myocardium (anti-bAm) and the left ventricular myocardium (anti-bVm) of the bovine heart. Cross-reactive antibodies were removed by cross-absorption. Absorbed anti-bAm and anti-bVm were specific for the myosin heavy chains when tested by enzyme immunoassay combined with SDS gel electrophoresis. Indirect immunofluorescence was used to determine the reactivity of atrial muscle fibers to the two antibodies. Three populations of atrial muscle fibers were distinguished in the bovine heart: (a) fibers reactive with anti-bAm and unreactive with anti-bVm, like most fibers in the left atrium; (b) fibers reactive with both antibodies, especially numerous in the right atrium; (c) fibers reactive with anti-bVm and unreactive with anti-bAm, present only in the interatrial septum and in specific regions of the right atrium, such as the crista terminalis. These findings can be accounted for by postulating the existence of two distinct types of atrial myosin heavy chains, one of which is antigenically related to ventricular myosin. The tendency for fibers labeled by anti-bVm to occur frequently in bundles and their preferential distribution in the crista terminalis, namely along one of the main conduction pathways between the sinus node and the atrioventricular node, and in the interatrial septum, where different internodal tracts are known to converge, suggests that these fibers may be specialized for faster conduction.