Cathodal Current Pulses Research Articles

New insights into the Belousov-Zhabotinskii reaction derived from EQCM measurements at a gold electrode

Electrochemical quartz crystal microbalance experiments were used to study the classical Belousov-Zhabotinskii (BZ) homogeneous oscillating system. This system involves 2 × 10(-3) M Ce(III), 0.28 M malonic acid and 0.063 M bromate as the main initial components in 1 M sulfuric acid solution. The gold-evaporated electrodes on a 10 MHz AT-cut quartz crystal were used for potentiometric and amperometric studies while the changes in crystal frequency provided mass data. Under open-circuit conditions, during the BZ reaction, oscillations of the gold electrode potential in the range ca. 0.8 to 1.07 V (SCE) with a period about 80 s occurred. They were accompanied by periodic 10-15 ng [i.e. ca. 45-70 ng cm(-2)] changes in the electrode mass. At more positive potentials a decrease in electrode mass occurred, while the mass increased at more negative potentials. At a constant applied electrode potential, corresponding to either the upper or the lower potential limit attained under open-circuit conditions, periodic pulses of cathodic current occurred and were accompanied by mass changes. A continuous decrease in the electrode mass occurred at 1.06 V. A detailed examination of the gold electrode behavior in the solutions containing individual components of the system using cyclic voltammetry and quartz crystal microgravimetry provided the information needed to interpret the mass changes that occur in the complete system. No significant changes in the electrode mass occurred in sulfuric acid solution in the potential range where current and mass oscillations take place in the full BZ reaction solution. The same result was found in sulfuric acid solutions containing either Ce(III) or malonic acid. Dissolution of gold occurred in a sulfuric acid solution containing bromate or bromide ions. Adsorption of bromide ions on gold electrode occurred in Br(-)-containing sulfuric acid solution at more negative potentials. In the BZ system, dissolution of gold in the presence of oxidizing (bromate) and complexing (bromide) species causes the decrease in the electrode mass that accompanies the positive potential jump under open-circuit conditions, or the current pulse that occurs at more negative applied constant potentials. Cathodic current pulses occurring at a constant electrode potential (either 0.8 or 1.06 V) are associated with the reduction of Ce(IV) formed as a result of periodic homogeneous oxidation of Ce(III) by bromate. Bromide ions formed in the course of the BZ reaction appear to play a significant role in electrode mass changes, causing a mass decrease at more positive potentials due to dissolution of gold, and a subsequent mass increase at more negative potentials due to adsorption processes.

Neural electrode degradation from continuous electrical stimulation: Comparison of sputtered and activated iridium oxide

The performance of neural electrodes in physiological fluid, especially in chronic use, is critical for the success of functional electrical stimulation devices. Tips of the Utah electrode arrays (UEAs) were coated with sputtered iridium oxide film (SIROF) and activated iridium oxide film (AIROF) to study the degradation during charge injection consistent with functional electrical stimulation (FES). The arrays were subjected to continuous biphasic, cathodal first, charge balanced (with equal cathodal and anodal pulse widths) current pulses for 7 h (>1 million pulses) at a frequency of 50 Hz. The amplitude and width of the current pulses were varied to determine the damage threshold of the coatings. Degradation was characterized by scanning electron microscopy, inductively coupled plasma mass spectrometry, electrochemical impedance spectroscopy and cyclic voltammetry. The injected charge and charge density per phase were found to play synergistic role in damaging the electrodes. The damage threshold for SIROF coated electrode tips of the UEA was between 60 nC with a charge density of 1.9 mC/cm 2 per phase and 80 nC with a charge density of 1.0 mC/cm 2 per phase. While for AIROF coated electrode tips, the threshold was between 40 nC with a charge density of 0.9 mC/cm 2 per phase and 50 nC with a charge density of 0.5 mC/cm 2 per phase. Compared to AIROF, SIROF showed higher damage threshold and therefore is highly recommended to be used as a stimulation material.

Measurement of total calcium by flash chronopotentiometry at polymer membrane ion-selective electrodes

Ionophore-based ion-selective electrodes are widely used for potentiometric electrolyte measurements, in which case they are known to detect the free ion activity. Total ion concentrations cannot be directly assessed by this methodology if the ion is predominantly present in a complexed form. We present here the direct measurement of total calcium using a calcium ion-selective electrode interrogated in a flash chronopotentiometric transduction mode. A high magnitude of cathodic current pulse is applied across a calcium ion-selective membrane containing the ionophore ETH 5234 but void of ion-exchanger to prevent spontaneous extraction. This induces a defined flux of calcium ions from the sample side to the membrane and results in the release of labile bound calcium and a concomitant depletion at the membrane surface at a critical current or time. This is observed as an inflection point on the potential–time curve and the square root of the transition time is linearly related to the total concentration in the sample. It is shown that the responses to solutions of labile calcium complexes of nitrilotriacetic acid (NTA) are in a good agreement with that of the same concentration of calcium chloride in saline solution with this protocol. Initial applications are aimed towards assaying extracellular calcium. Calcium binding to albumin is shown to be inconsequential with sample dilutions typical for clinical assays. Calcium calibration curves in real and artificial dilute serum are finally shown to correspond to that of calcium chloride, suggesting that the methodology is indeed capable of detecting total calcium under these conditions. The present membrane materials allow detection of up to over 0.5 mM total calcium in serum, currently requiring such samples to be diluted about 5-fold. The slopes of the square root of time–concentration dependence for the calibrations of free calcium in a background of NaCl and total serum calcium were found to be 3.857 and 3.717 s 1/2 mM −1, respectively, deviating by just 3.6%. The lower detection limit (3× SD) was calculated as 12 μM.

Activation of ganglion cells in wild-type and rd1 mouse retinas with monophasic and biphasic current pulses

We and other research groups are designing an electronic retinal prosthesis to provide vision for patients who are blind due to photoreceptor degeneration. In this study, we examined the effect of stimulus waveform on the amount of current needed to activate retinal ganglion cells (RGCs) when the retinal neural network is stimulated. Isolated retinas of wild-type and rd1 mice were stimulated with cathodal and anodal monophasic current pulses of 1 ms duration and symmetric biphasic current pulses (1 ms per phase) delivered through an electrode that was located subretinally. For both wild-type and rd1 mouse retinas, cathodal current pulses were least effective in activating most RGCs. The median threshold current for a cathodal current pulse was 2.0–4.4 fold higher than the median threshold current for either an anodal or a biphasic current pulse. In wild-type mouse retinas, the median threshold current for activating RGCs with anodal current pulses was 23% lower than that with biphasic current pulses. In rd1 mouse retinas, the median threshold currents for anodal and biphasic current pulses were about the same. However, the variance in thresholds of rd1 RGCs for biphasic pulse stimulation was much smaller than for anodal pulse stimulation. Thus, a symmetric biphasic current pulse may be the best stimulus for activating the greatest number of RGCs in retinas devoid of photoreceptors.

Flash chronopotentiometric sensing of the polyions protamine and heparin at ion-selective membranes

We report here on a highly sensitive and rapid detection technique, multipulse flash chronopotentiometry, for the anticoagulant polyion heparin and its antidote protamine. The technique is based on a localized titration of the polyions at the surface of an appropriately formulated polymeric ion-selective membrane devoid of ion exchange properties to prohibit spontaneous extraction processes. A defined ion flux from the sample side to the membrane is induced electrochemically by applying a current pulse of appropriate amplitude and sign. The resulting depletion of the measured ions at the membrane surface gives rise to a characteristic limiting current or transition time and is observed as an inflection point in the resulting chronopotentiogram. The limiting current and the square root of the transition time are linear functions of the concentration of the polyion and yield sensitive and rapid analytical information attractive for clinical diagnostics applications. The polyion protamine is detected in 10-fold diluted blood samples in a matter of seconds via a cathodic current pulse. The utility of the technique for monitoring heparin/protamine titrations in physiological saline solutions is demonstrated.

A role of electrical inhibition in sensorimotor integration

Although it is accepted that extracellular fields generated by neuronal activity can influence the excitability of neighboring cells, whether this form of neurotransmission has a functional role remains open. In vivo field effects occur in the teleost Mauthner (M)-cell system, where a combination of structural features support the concept of inhibitory electrical synapses. A single spike in one M-cell evoked within as little as 2.2 ms of the onset of an abrupt sound, simulating a predatory strike, initiates a startle-escape behavior [Zottoli SJ (1977) J Exp Biol 66:243-254]. We show that such sounds produce synchronized action potentials in as many as 20 or more interneurons that mediate feed-forward electrical inhibition of the M-cell. The resulting action currents produce an electrical inhibition that coincides with the electrotonic excitatory drive to the M-cell; the amplitude of the peak of the inhibition is approximately 40% of that of the excitation. When electrical inhibition is neutralized with an extracellular cathodal current pulse, subthreshold auditory stimuli are converted into ones that produce an M-spike. Because the timing of electrical inhibition is often the same as the latency of M-cell firing in freely swimming fish, we conclude that electrical inhibition participates in regulating the threshold of the acoustic startle-escape behavior. Therefore, a field effect is likely to be essential to the normal functioning of the neural network.

Direct sensing of total acidity by chronopotentiometric flash titrations at polymer membrane ion-selective electrodes.

Polymer membrane ion-selective electrodes containing lipophilic ionophores are traditionally interrogated by zero current potentiometry, which, ideally, gives information on the sample activity of ionic species. It is shown here that a discrete cathodic current pulse across an H (+)-selective polymeric membrane doped with the ionophore ETH 5294 may be used for the chronopotentiometric detection of pH in well-buffered samples. However, a reduction in the buffer capacity leads to large deviations from the expected Nernstian response slope. This is explained by the local depletion of hydrogen ions at the sample-membrane interface as a result of the galvanostatically imposed ion flux in direction of the membrane. This depletion is found to be a function of the total acidity of the sample and can be directly monitored chronopotentiometrically in a flash titration experiment. The subsequent application of a baseline potential pulse reverses the extraction process of the current pulse, allowing one to interrogate the sample with minimal perturbation. In one protocol, total acidity is found to be proportional to the magnitude of applied current at the flash titration end point. More conveniently, the square root of the flash titration end point time observed at a fixed applied current is a linear function of the total acid concentration. This suggests that it is possible to perform rapid localized pH titrations at ion-selective electrodes without the need for volumetric titrimetry. The technique is explored here for acetic acid, MES and citric acid with promising results. Polymeric membrane electrodes based on poly(vinyl chloride) plasticized with o-nitrophenyl octyl ether in a 1:2 mass ratio may be used for the detection of acids of up to ca. 1 mM concentration, with flash titration times on the order of a few seconds. Possible limitations of the technique are discussed, including variations of the acid diffusion coefficients and influence of electrical migration.

Multicriteria optimization of mechanical and morphological properties of chromium electrodeposits under reverse pulse plating

In this work, a central composite design experiment was performed to estimate the effect of the electroplating parameters (temperature of electrolyte, cathodic and anodic pulse current densities, and cathodic and anodic pulse lengths,) on four properties of hard chromium electrodeposits. The studied responses were the hardness (Hv), the roughness quantified by the two criteria Ra (nm) and R (μm)), and the specific abrasive energy, Es (μJ μm−3). Analysis of the responses using optimal path technique did not lead to a common set of experimental conditions which fulfilled the required properties. Thus, the desirability function approach has been employed in order to find the best compromise between the different experimental responses. The optimal conditions are: electrolyte temperature: 49.9 °C; cathodic pulse current density: 42.0 A dm−2; anodic pulse current density: 51.5 A dm−2, cathodic pulse length: 6.23 s and anodic pulse length: 28.5 ms. Under these conditions, the estimated response values are 738 Hv, 262 nm, 2.61 μm and 0.027 μJ μm−3 for hardness, Ra, R and specific abrasive energy respectively, validated experimentally. The resultant coating, examined by AFM, exhibits a nodular fine-grained morphology.

The influence of electrolyte composition on the in vitro charge-injection limits of activated iridium oxide (AIROF) stimulation electrodes

The effects of ionic conductivity and buffer concentration of electrolytes used for in vitro measurement of the charge-injection limits of activated iridium oxide (AIROF) neural stimulation electrodes have been investigated. Charge-injection limits of AIROF microelectrodes were measured in saline with a range of phosphate buffer concentrations from [PO43−] = 0 to [PO43−] = 103 mM and ionic conductivities from 2–28 mS cm−1. The charge-injection limits were insensitive to the buffer concentration, but varied significantly with ionic conductivity. Using 0.4 ms cathodal current pulses at 50 Hz, the charge-injection limit increased from 0.5 mC cm−2 to 2.1 mC cm−2 as the conductivity was increased from 2 mS cm−1 to 28 mS cm−1. An explanation is proposed in which the observed dependence on ionic conductivity arises from non-uniform reduction and oxidation within the porous AIROF and from uncorrected iR-drops that result in an overestimation of the redox potential during pulsing. Conversely, slow-sweep-rate cyclic voltammograms (CVs) were sensitive to buffer concentration with the potentials of the primary Ir3+/Ir4+ reduction and oxidation reactions shifting ∼300 mV as the buffer concentration decreased from [PO43−] = 103 mM to [PO43−] = 0 mM. The CV response was insensitive to ionic conductivity. A comparison of in vitro AIROF charge-injection limits in commonly employed electrolyte models of extracellular fluid revealed a significant dependence on the electrolyte, with more than a factor of 4 difference under some pulsing conditions, emphasizing the need to select an electrolyte model that closely matches the conductivity and ionic composition of the in vivo environment.

Thresholds for activation of rabbit retinal ganglion cells with a subretinal electrode

The ultimate success of a retinal prosthesis to create vision will likely depend upon developing a base of knowledge of how best to electrically stimulate the retina. Previously, we studied the responses of rabbit retinal ganglion cells (RGCs) to current pulses applied with an electrode placed on the epiretinal surface. In the present study, we examined the responses of rabbit RGCs to current pulses applied with a subretinal electrode. Single-unit extracellular recordings were made from OFF RGCs and ON RGCs in isolated retinas, which were stimulated with monophasic current pulses (0.1–50 ms in duration), delivered through a 500-μm diameter electrode. All RGCs elicited one or more bursts of action potentials upon electrical stimulation of the retina. The timing of the bursts depended upon both the polarity of the electrical stimulus and the RGC type. With near-threshold current pulses, the response latencies of OFF RGCs to anodal stimulation were comparable to those of ON RGCs to cathodal stimulation, whereas the response latencies of OFF RGCs to cathodal stimulation were comparable to those of ON RGCs to anodal stimulation. Threshold currents for activation of RGCs decreased with increased pulse duration. For OFF RGCs, threshold currents for cathodal current pulses were, on average, 2–7.5 times higher (depending upon pulse duration) than the threshold currents for anodal current pulses. For ON RGCs, threshold currents for cathodal and anodal current pulses were, on average, nearly identical for all pulse durations and were equivalent to threshold currents of OFF RGCs to anodal stimulation. With respect to a subretinal prosthesis, our findings suggest the possibility that cathodal current pulses may bias activation of ON RGCs in blind patients.

Carbon Nanotube Based Electrodes for Neuroprosthetic Applications

ABSTRACTFoster-Miller, Inc., in conjunction with InnerSea Technology, NanoTechLabs and Dr. Lois Robblee, has demonstrated a simple, low cost process for the fabrication of high capacitance, low impedance, and high surface area carbon nanotube (CNT) electrodes for use as implantable microelectrodes. Implantable microelectrodes for electrical stimulation of neurons and recording neuronal responses are essential tools for neurophysiologists studying the behavior of neurons in the brain, spinal cord and peripheral nerve. Critical properties of an electrode interface should include: low noise, low impedance, biocompatibility, electrical stability during chronic use, and high charge capacity. Iridium oxide has all of these properties and thus has been utilized for significant developments in the neural prostheses area. However, these electrodes have several shortcomings, including: high material cost, labor-intensive processing, and deterioration of long term stability.The results of electrochemical testing of the CNT electrodes show high capacitance and low impedance. Preliminary testing indicates that the CNT felt electrodes have advantages over state of the art iridium oxide electrodes in that their highest charge capacity is distributed within the cathodic portion of the water window, exactly where iridium oxide charge capacity is lowest. When the integration of the cathodic part of a CV is done in the potential window from 0.3 V (open circuit) to −0.7 V, at which the electrode will be used, we obtain a value of 38 μc-cm−2. Similar integration for an iridium oxide electrode gives a value of 15 mC cm−2. The high charge capacity of the CNT felt electrode over the cathodic potential range below 0.0 V is advantageous for electrical stimulation with cathodal current pulses. This is a feature lacking in Iridium oxide electrodes for which most of the charge capacity is accessed over anodic potentials above 0.0 V. In order for Iridium oxide electrodes to utilize their charge capacity during cathodal pulses, it is necessary to apply an anodic bias to the stimulation electrode between stimulus pulses. This leads to increased complexity of stimulation circuitry and the possibility of the intermittent occurrence of low dc current, both of which will be avoided with the CNT felt electrodes.

In Vitro Comparison of the Charge-Injection Limits of Activated Iridium Oxide (AIROF) and Platinum-Iridium Microelectrodes

The charge-injection limits of activated iridium oxide electrodes (AIROF) and PtIr microelectrodes with similar geometric area and shape have been compared in vitro using a stimulation waveform that delivers cathodal current pulses with current-limited control of the electrode bias potential in the interpulse period. Charge-injection limits were compared over a bias range of 0.1-0.7 V (versus Ag/AgCl) and pulse frequencies of 20, 50, and 100 Hz. The AIROF was capable of injecting between 4 and 10 times the charge of the PtIr electrode, with a maximum value of 3.9 mC/cm2 obtained at a 0.7 V bias and 20 Hz frequency.

A variable range bi-phasic current stimulus driver circuitry for an implantable retinal prosthetic device

This paper reports a driver circuitry to generate bi-phasic (anodic and cathodic) current pulses for stimulating the retinal layer through electrodes which is part of a retinal prosthetic device for implants in blind patients affected by retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Dual voltage architecture is used to halve the number of interface leads from the chip to the stimulation sites compared to a single voltage supply. The driver circuitry is designed to deliver currents with six bit resolution for a wide range of full scale currents up to 600 /spl mu/A. To cater to the varying stimulus requirements among patients and different regions of the retina, variable gain architecture is used to achieve fine resolution even for a narrow range of stimulus. 1:8 demultiplexing feature is embedded within the output stage thus allowing one DAC for eight outputs. A novel charge cancellation circuitry with current limiting capability is implemented to discharge the electrodes for medical safety. Measurement results of a prototype chip fabricated in 1.5-/spl mu/m CMOS technology are presented.

Responses of rabbit retinal ganglion cells to electrical stimulation with an epiretinal electrode

Rational selection of electrical stimulus parameters for an electronic retinal prosthesis requires knowledge of the electrophysiological responses of retinal neurons to electrical stimuli. In this study, we examined the effects of cathodal and anodal current pulses on the extracellularly recorded responses of OFF and ON rabbit retinal ganglion cells (RGCs) in an in vitro preparation. Current pulses (1 msec duration), delivered by a 125 µm electrode placed on the inner retinal surface within the receptive field of a RGC, produced both short-latency (⩽5 msec) and long-latency (8–60 msec) responses. The long-latency responses, but not the short-latency responses, were abolished upon application of the glutamate receptor antagonists CNQX and NBQX, thus indicating that the long-latency responses of RGCs are due to activation of presynaptic neurons in the retina. The latency of the long-latency response depended upon the polarity of the stimulus. For OFF RGCs, the average latency was 11 msec for a cathodal stimulus and 24 msec for an anodal stimulus. For ON RGCs, the average latency was 25 msec for a cathodal stimulus and 16 msec for an anodal stimulus. The threshold current also depended upon the polarity of the stimulus, at least for OFF RGCs. The average threshold current for evoking a long-latency response in OFF RGCs was 10 µA for a cathodal stimulus and 21 µA for an anodal stimulus. In ON RGCs, the average threshold current was 13 µA for a cathodal stimulus and 15 µA for an anodal stimulus.

Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode.

To determine electrical thresholds required for extracellular activation of retinal ganglion cells as part of a project to develop an epiretinal prosthesis. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100- micro s duration were delivered to the inner surface of the retina from a 5- micro m long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one half) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation.

Response properties of the refractory auditory nerve fiber.

The refractory characteristics of auditory nerve fibers limit their ability to accurately encode temporal information. Therefore, they are relevant to the design of cochlear prostheses. It is also possible that the refractory property could be exploited by prosthetic devices to improve information transfer, as refractoriness may enhance the nerve's stochastic properties. Furthermore, refractory data are needed for the development of accurate computational models of auditory nerve fibers. We applied a two-pulse forward-masking paradigm to a feline model of the human auditory nerve to assess refractory properties of single fibers. Each fiber was driven to refractoriness by a single (masker) current pulse delivered intracochlearly. Properties of firing efficiency, latency, jitter, spike amplitude, and relative spread (a measure of dynamic range and stochasticity) were examined by exciting fibers with a second (probe) pulse and systematically varying the masker-probe interval (MPI). Responses to monophasic cathodic current pulses were analyzed. We estimated the mean absolute refractory period to be about 330 micros and the mean recovery time constant to be about 410 micros. A significant proportion of fibers (13 of 34) responded to the probe pulse with MPIs as short as 500 micros. Spike amplitude decreased with decreasing MPI, a finding relevant to the development of computational nerve-fiber models, interpretation of gross evoked potentials, and models of more central neural processing. A small mean decrement in spike jitter was noted at small MPI values. Some trends (such as spike latency-vs-MPI) varied across fibers, suggesting that sites of excitation varied across fibers. Relative spread was found to increase with decreasing MPI values, providing direct evidence that stochastic properties of fibers are altered under conditions of refractoriness.

Electrodeposition of compositionally modulated alloys by a electrodeposition–displacement reaction method

A method for the electrodeposition of compositionally modulated alloys by a electrodeposition–displacement reaction scheme from a single electrolyte using pulsed currents is presented. The less noble material is deposited by applying a high cathodic current pulse. The more noble component is plated by a displacement reaction between the more noble and the less noble components when the current is switched off. Theoretical equations to calculate the composition of the modulated layers are discussed. Experimentally, modulated alloys of copper and nickel have been plated to illustrate the applicability of this scheme.

Activation of calcium-dependent chloride channels causes post-tetanic depolarization in rabbit parasympathetic neurons

Intracellular recordings were made from neurons in rabbit and feline vesical parasympathetic ganglia in vitro. In response to cathodal current injection (0.1–1 nA for 2–20 ms) the majority of rabbit neurons (229 out of 250) exhibited a single action potential that was followed by a fast and slow after-hyperpolarization (sAHP neuron). The remainder of the cells exhibited an action potential followed by only a fast after-hyperpolarization (fAHP neuron). fAHP neurons did not exhibit anomalous rectification and a spontaneous rhythmic hyperpolarization, which were common membrane properties in sAHP neurons. In response to a train of cathodal current pulses (5–20 Hz for 0.1–10 s), fAHP neurons exhibited action potentials followed by a post-tetanic depolarization (PTD). The PTD was associated with a decrease in membrane input resistance. The amplitude and duration of the PTD were a function of the number of action potentials in the train. The amplitude of the PTD was increased by membrane hyperpolarization and its estimated reversal potential was approximately −30 mV. Low-chloride solution and intracellular injection of chloride ions augmented the amplitude and duration of the PTD, whereas low-sodium, high-potassium and low-potassium solutions did not affect them. Tetraethylammonium (5–10 mM) and barium (0.5–1 mM) increased the amplitude and duration of the PTD. Nominal calcium-free solutions and ω-conotoxin (500 nM) abolished the PTD. The data suggest that activation of chloride channels by calcium influx through ω-conotoxin-sensitive calcium channels mediates the PTD. Repetitive stimulation of the pelvic nerve evoked a train of orthodromic action potentials followed by the PTD of fAHP neurons. (+)-Tubocurarine (10 μM) and hexamethonium (200 μM), but not atropine (1 μM), abolished orthodromic action potentials and the PTD, whereas these cholinergic antagonists did not depress the PTD evoked by direct action potentials. In summary, the data suggest that the PTD may function as a slow synaptic potential in fAHP neurons. This appears likely because neither slow excitatory nor inhibitory postsynaptic potentials are present in neurons of rabbit vesical parasympathetic ganglia. In contrast, slow inhibitory and excitatory postsynaptic potentials were recorded from neurons in feline vesical parasympathetic ganglia.

Desynchronization of epileptiform activity by extracellular current pulses in rat hippocampal slices.

1. A single cathodic current pulse applied in the somatic CA1 region of the hippocampus was found to induce a large decrease in the amplitude of the population spike. 2. Intracellular recordings showed intense cellular firing suggesting the amplitude decrease could not be attributed to a decrease in neuronal firing. 3. Simultaneous intracellular and extracellular potentials were recorded to analyse the synchronization of neuronal firing in the CA1 region. Action potentials were synchronized with the first population spike but this synchronization decreased with subsequent spikes. Histograms of the phase of the action potentials displayed a normal distribution. 4. Histograms of the phases of the action potentials following the application of the 'singular stimulus' (one producing a singular response) revealed a uniform distribution of the phases suggesting that the neuronal population was desynchronized. 5. This desynchronization effect of the singular stimulus was verified by double intracellular recordings. The simultaneous firing of two neurons could be desynchronized by the application of the singular stimulus. 6. These findings indicate that it is possible to desynchronize a neuronal pool with the application of a single current pulse. In addition, the results show that it is possible for a neuronal population to fire a large number of action potentials with no resulting evoked potentials in the extracellular space.

Valproic acid inhibits the depolarizing rectification in neurons of rat amygdala

The actions of valproic acid (VPA) on neuronal membrane properties and synaptic transmission were studied using intracellular recording techniques in rat basolateral neurons of the amygdala slices. In therapeutically attainable concentrations (10-100 microM), VPA decreased synaptically-induced epileptiform bursting in the presence of bicuculline. Additionally, the frequency of repetitive discharge induced by direct superthreshold depolarizing current pulses was decreased by VPA. However, evoked excitatory and inhibitory postsynaptic potentials were not affected at this level of drug concentration. The current-voltage relationship of untreated neurons revealed rectification of membrane potential when neuronal membrane was depolarized with cathodal current pulses. This depolarizing rectification was blocked by VPA. High medium calcium or addition of the sodium channel blocker tetrodotoxin (TTX) also blocked the depolarizing rectification, whereas the calcium channel antagonist diltiazem had no effect on the rectification. Elevation of medium calcium concentration also blocked the bicuculline-induced bursting. These results indicate that the inhibition by VPA of subthreshold slow sodium current and membrane depolarizing rectification results in suppression of neuronal membrane excitability which is probably a major mechanism for its anticonvulsant action.