Spread Of Electrical Signals Research Articles

Effect of Carvacrol, TRP Channels Modulator, on Cardiac Electrical Activity.

Despite the wide application of carvacrol (CAR) in medicines, dietary supplements, and foods, there is still insufficient electrophysiological data on the mechanisms of action of CAR, particularly with regard to heart function. Therefore, in this study, we attempted to elucidate whether CAR, whose inhibitory effect on both cardiac and vascular TRPM7 and L-type Ca2+ currents has been demonstrated previously, could modify cardiac electrical activity. We used a combination of optical mapping and microelectrode techniques to track the action potentials (APs) and the spread of electrical activity in a Langendorff-perfused rabbit heart model during atrial/endo/epicardial pacing. Simultaneously, ECG recordings were acquired. Because human trials on CAR are still lacking, we tested the action of CAR on human ventricular preparations obtained from explanted hearts. Activation time (AT), AP duration (APD), and conduction velocity maps were constructed. We demonstrated that at a low concentration (10 μM) of CAR, only marginal changes in the AP parameters were observed. At higher concentrations (≥100 μM), a decrease in AP upstroke velocity (dV/dtmax), suggesting inhibition of Na+ current, and APD (at 50 and 90% repolarization) was detected; also slowing in the spread of electrical signals via the atrioventricular node was observed, suggesting impaired functioning of Ca2+ channels. In addition, a decrease in the T-wave amplitude was seen on the ECG, suggesting an impaired repolarization process. Nevertheless, those changes occurred without a significant impact on the resting membrane potential and were reversible. We suggest that CAR might play a role in modulating cardiac electrical activity at high concentrations.

Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating.

We combined the Hodgkin–Huxley equations and a 36-state model of gap junction channel gating to simulate electrical signal transfer through electrical synapses. Differently from most previous studies, our model can account for dynamic modulation of junctional conductance during the spread of electrical signal between coupled neurons. The model of electrical synapse is based on electrical properties of the gap junction channel encompassing two fast and two slow gates triggered by the transjunctional voltage. We quantified the influence of a difference in input resistances of electrically coupled neurons and instantaneous conductance–voltage rectification of gap junctions on an asymmetry of cell-to-cell signaling. We demonstrated that such asymmetry strongly depends on junctional conductance and can lead to the unidirectional transfer of action potentials. The simulation results also revealed that voltage spikes, which develop between neighboring cells during the spread of action potentials, can induce a rapid decay of junctional conductance, thus demonstrating spiking activity-dependent short-term plasticity of electrical synapses. This conclusion was supported by experimental data obtained in HeLa cells transfected with connexin45, which is among connexin isoforms expressed in neurons. Moreover, the model allowed us to replicate the kinetics of junctional conductance under different levels of intracellular concentration of free magnesium ([Mg2+]i), which was experimentally recorded in cells expressing connexin36, a major neuronal connexin. We demonstrated that such [Mg2+]i-dependent long-term plasticity of the electrical synapse can be adequately reproduced through the changes of slow gate parameters of the 36-state model. This suggests that some types of chemical modulation of gap junctions can be executed through the underlying mechanisms of voltage gating. Overall, the developed model accounts for direction-dependent asymmetry, as well as for short- and long-term plasticity of electrical synapses. Our modeling results demonstrate that such complex behavior of the electrical synapse is important in shaping the response of coupled neurons.

Recent advances in the study of endothelium-dependent hyperpolarizing factor (EDHF)

Recent advances in the properties and physiological functions of endothelium-dependent hyperpolarizing factor (EDHF) in vascular tissues were reviewed briefly. The EDHF-induced hyperpolarization is inhibited by charybdotoxin, indicating that the potential is produced mainly by activation of intermediate conductance Ca-sensitive K-channels. During generation of EDHF responses, endothelial Ca2+ concentration was elevated, suggesting that the activated K-channels were distributed on the endothelial membrane. This was confirmed by direct recording of membrane potentials from endothelial and smooth muscle cells using double patch electrodes. Measurement of the propagation of potentials applied to endothelial or smooth muscle cells to surrounding cells revealed that there were tight electrical connections between endothelial cells much more than between endothelial and smooth muscle cells or between smooth muscle cells, and these observations yielded a possible spread of electrical signal along the endothelial layer first, and then the signals would be conducted to smooth muscle cell layers. These properties of vascular tissues allow speculating that EDHF is an electrical signal propagated from endothelial cells electrotonically through myoendothelial gap junctions. Several candidates have been proposed as EDHF, and possibilities of individual substances for EDHF were discussed. The cellular mechanism of the hyperpolarization-induced vasodilatation remains unclear, and this should be clarified in the future for further understanding of the EDHF-induced vasodilatation.

Activity-dependent changes in intracellular calcium in myenteric neurons.

The spatial distribution and changes in intracellular calcium concentration ([Ca2+]i) in myenteric neurons were measured using fura 2 in the longitudinal muscle-myenteric plexus preparation from the guinea pig duodenum. These measurements were made simultaneously with intracellular voltage recordings. The generation of action potentials in the cell bodies of both S- and AH-type neurons increased [Ca2+]i in the processes and cell bodies. There was no measurable delay between the [Ca2+]i changes in the somata and the processes, indicating that these changes were caused by the spread of electrical signals and not by diffusion. The rate of Ca2+ removal was faster in the processes than in the somata, apparently due to the large surface-to-volume ratio in the former. In AH neurons, the [Ca2+]i transient was shorter than the duration of the after-spike hyperpolarization. It is concluded that the two main types of myenteric neurons possess voltage-gated Ca2+ channels in both somata and processes.

Electrotonic architecture of hippocampal CA1 pyramidal neurons based on three-dimensional reconstructions.

1. The spread of electrical signals in pyramidal neurons from the CA1 field of rat hippocampus was investigated through multicompartmental modeling based on three-dimensional morphometric reconstructions of four of these cells. These models were used to dissect the electrotonic architecture of these neurons, and to evaluate the equivalent cylinder approach that this laboratory and others have previously applied to them. Robustness of results was verified by the use of wide ranges of values of specific membrane resistance (Rm) and cytoplasmic resistivity. 2. The anatomy exhibited extreme departures from a key assumption of the equivalent cylinder model, the so-called "3/2 power law." 3. The compartmental models showed that the frequency distribution of steady-state electrotonic distances between the soma and the dendritic terminations was multimodal, with a large range and a sizeable coefficient of variation. This violated another central assumption of the equivalent cylinder model, namely, that all terminations are electronically equidistant from the soma. This finding, which was observed both for "centrifugal" (away from the soma) and "centripetal" (toward the soma) spread of electrical signals, indicates that the concept of an equivalent electrotonic length for the whole dendritic tree is not appropriate for these neurons. 4. The multiple peaks in the electrotonic distance distributions, whether for centrifugal or centripetal voltage transfer, were clearly related to the laminar organization of synaptic afferents in the CA1 region. 5. The results in the three preceding paragraphs reveal how little of the electrotonic architecture of these neurons is captured by a simple equivalent cylinder model. The multicompartmental model is more appropriate for exploring synaptic signaling and transient events in CA1 pyramidal neurons. 6. There was significant attenuation of synaptic potential, current, and charge as they spread from the dendritic tree to the soma. Charge suffered the least and voltage suffered the most attenuation. Attenuation depended weakly on Rm and strongly on synaptic location. Delay of time to peak was more distorted for voltage than for current and was more affected by Rm. 7. Adequate space clamp is not possible for most of the synapses on these cells. Application of a somatic voltage clamp had no significant effect on voltage transients in the subsynaptic membrane. 8. The possible existence of steep voltage gradients within the dendritic tree is consistent with the idea that there can be some degree of local processing and that different regions of the neuron may function semiautonomously. These spatial gradients are potentially relevant to synaptic plasticity in the hippocampus, and they also suggest caution in interpreting some neurophysiological results.

Behaviour of the rod network in the tiger salamander retina mediated by membrane properties of individual rods.

1. The spread of electrical signals between rods in the salamander retina was examined by passing current into one rod and recording the voltage responses in nearby rods. Rod network behaviour, measured in this way, was simulated from data on rod membrane properties gathered in voltage-clamp experiments on single isolated rods.2. The network voltage responses to square current pulses became smaller, more transient, and had a longer time-to-peak, for rods further away from the site of current injection. Depolarizing currents produced smaller responses than hyperpolarizing currents of the same magnitude.3. Neighbouring rods and cones were coupled less strongly than neighbouring rods.4. The response of the rod network to current injection was unaffected by 2 mm-aspartate(-), which eliminates transmission from receptors to horizontal cells.5. The input resistance of single isolated rods, measured at the resting potential, varied between 100 and 680 MOmega. The lower values were probably due to damage by the micro-electrodes. Electrical coupling was found to be very strong between the rod inner and outer segments.6. A strong ;instantaneous' outward rectification seen in isolated rods at potentials positive to -35 mV was reduced, but not abolished, by 15 mm-TEA.7. In normal solution, isolated rods exhibited a voltage- and time-dependent current, I(A), whose kinetics were approximated by a single first-order gating variable, and whose activation curve spanned the range between -40 and -80 mV. The time constant for the current varied with voltage and was 60-200 msec between -140 and -40 mV.8. A reversal potential for I(A) could not be found between -140 and -40 mV in normal solution, and the fully activated current, I(A), was approximately voltage-independent, with a magnitude of approximately 0.1 nA over this potential range.9. By several criteria, I(A) behaved as a single inward current activated by hyperpolarization. Pharmacological studies suggest, however, that it is the sum of at least two currents with very similar kinetics.10. Most isolated rods exhibited a very slow (tau approximately 3 sec) increase in net outward current on depolarizing beyond -35 mV. The magnitude of this current varied considerably between cells.11. Assuming that the rod network can be approximated by a square lattice of individual rods, resistively coupled together, the voltage-clamp data on isolated rods were used to predict the response of the network to current injection at one cell. The theoretical and observed network behaviour were in good agreement. The resistance coupling neighbouring rods was estimated to be approximately 300 MOmega. The current I(A) plays a major role in determining the behaviour of the rod network.12. The time-dependent current, I(A), is responsible for the peak-plateau wave form of the response to a bright flash. A current similar to I(A) could also account for the negative propagation velocity of the peak of the dim flash response, through the rod network of the turtle, observed by Detwiler, Hodgkin & McNaughton (1978).