Model study of the spread of electrotonic potential in cardiac tissue

This model study describes the electrotonic response of a cable model of cardiac tissue stimulated at one point. The stimulus is applied intracellularly in the form of a 2ms pulse of current of near threshold amplitude. The attenuation of the electrotonic potential with distance and its mode of propagation along the cable are compared for equivalent passive, continuous and discontinuous cables. The three structures have the same basic physical and electrical characteristic and they differ either with respect to being active or passive or to the presence or absence of intercellular gap junctions. In the continuous cable a just subthreshold stimulus produces a local active response which propagates more slowly and is attenuated less rapidly with distance than in a passive cable. The spatial decrement of the local response in a discontinuous cable is faster than in a continuous cable of equal average resistivity. It is suggested that the larger time constant of the foot of the action potential observed in the longitudinal direction in cardiac muscle could be due in part to the electrotonic spread of the local response from the site of stimulation.     

Electrical responses of smooth muscle to external stimulation in hypertonic solution

1. The electrical responses of single smooth muscle cells of the guinea-pig taenia coli to external stimulation were studied in two times hypertonic solution and compared with the responses to intracellular stimulation.2. Exposure to Krebs solution made two times hypertonic by adding sucrose abolished the mechanical movement and stopped the spontaneous electrical activity. The electrical response to stimulation was essentially similar to that in physiological solution.3. When the tissue was placed between stimulating electrodes, the cells near the cathode were depolarized and produced spikes, while the cells near the anode were hyperpolarized and produced small spikes only with weak stimuli. The cells near the centre were not polarized but produced spikes with a frequency pattern similar to that near the cathode.4. When both stimulating electrodes were put close together at one end of the tissue, the intracellularly recorded extrapolar polarization changed its polarity at 1-2 mm distance from the stimulating electrode. When an insulating partition was placed between the stimulating and recording site, the reversed polarity was no longer observed and the electrotonic potential spread decayed roughly exponentially with distance from the stimulating electrode. The time course of the electrotonic potential was similar to that predicted from the cable equation applied to nerve. The space constant was 1.68 +/- 0.08 mm (S.E. of mean) and the time constant was 60-100 msec. The cable properties may be explained by assuming that many fibres, connected in series and in parallel, are aggregated as functional units.5. The strength-duration curve was a simple hyperbola and the chronaxie was about 20 msec. The relation between extracellularly applied current and intracellularly recorded potential showed that membrane resistance decreased with depolarization and slightly increased with hyperpolarization. The spike was propagated in both directions at the same speed as in physiological solution (7.3 +/- 0.7 cm/sec).6. Long anodal current often produced electrical activity of low amplitude which seemed to be due to the spike activity near the cathode, because the same frequency modulation was seen in both activities, and external hyperpolarization reduced the size of the propagated spike. Cessation of a strong and long anodal current was followed by slow depolarization, about 1 sec in duration and up to 10 mV in amplitude, which sometimes triggered a spike.7. The difference between responses to intracellular and to external stimulation may be explained by assuming that different parts of the cell membrane have different electrical properties. They may be: A, areas of close apposition between cells; B, areas capable of generating the slow component; C, an area capable of producing the spike, but less excitable.     

The propagation of transient potentials in some linear cable structures

1. Analytical solutions have been given for the time course of voltage transients occurring in one-dimensional cable structures, with linear uniform membrane properties.2. These solutions show how the time course of the voltage transients generated at different distances are affected by variations in the time course of current injection (at one point on the cable) and by alterations in the length of the cable, with either sealed or open end terminations. These effects are illustrated with computed results.3. Simple measurements from the time course of a membrane potential displacement, occurring in a one-dimensional cable structure following a brief current injection across the membrane, are used to evaluate the parameters which describe the cable model. These parameters are the membrane time constant, the electrotonic length of the cable, the cable end termination, and in the case of a post-synaptic potential, the distance between the electrode and the active synapse.     

Effect of a perfusing bath on the rate of rise of an action potential propagating through a slab of cardiac tissue

Experiments show that the rate of rise of the action potential depends on the direction of propagation in cardiac tissue. Two interpretations of these experiments have been presented: (i) the data are evidence of discrete propagation in cardiac tissue, and (ii) the data are an effect of the perfusing bath. In this paper we present a mathematical model that supports the second interpretation. We use the bidomain model to simulate action potential propagation through a slab of cardiac tissue perfused by a bath. We assume an intracellular potential distribution and solve the bidomain equations analytically for the transmembrane and extracellular potentials. The key assumption in our model is that the intracellular potential is independent of depth within the tissue. This assumption ensures that all three boundary conditions at the surface of a bidomain are satisfied simultaneously. One advantage of this model over previous numerical calculations is that we obtain an analytical solution for the transmembrane potential. The model predicts that the bath reduces the rate of rise of the transmembrane action potential at the tissue surface, and that this reduction depends on the direction of propagation. The model is consistent with the hypothesis that the perfusing bath causes the observed dependence of the action-potential rate of rise on the direction of propagation, and that this dependence has nothing to do with discrete properties of cardiac tissue.     

New aspects of vulnerability in heterogeneous models of ventricular wall and its modulation by loss of cardiac sodium channel function

This numerical study quantified the vulnerable period (VP) in heterogeneous models of the cardiac ventricular wall and its modulation by loss of cardiac sodium channel function (NaLOF). According to several articles, NaLOF prolongs the VP and therefore increases the risk of re-entrant arrhythmias, but the studies used uniform models, neglecting spatial variation of action potential duration (APD). Here, physiological transmural heterogeneity was introduced into one-dimensional cables of the Luo-Rudy model cells. Based on the results with paired S1–S2 stimulation, a generalised formula for the VP was proposed that takes into account APD dispersion, and new phenomena pertaining to the VP are described that are not present in homogeneous excitable media. Under normal conditions, the vulnerable period in the heterogeneous cable media. Under normal conditions, the vulnerable period in the heterogeneous cable with M cells was in the range of 0–21 ms, depending on S2 localisation, but only 2,4 ms throughout the uniform fibre. Unidirectional propagation induced during the VP could be antegrade or retrograde, depending on the localisation of the test stimulus and cable parameters, but, in a uniform model, it was always in the retrograde direction. Reduced sodium channel conductance from control 16 mS μF⁻¹ to 4mS μF⁻¹ decreased the maximum VP to 11 ms in the heterogeneous cable, but increased the VP to 3 ms in the homogeneous model. It was concluded that realistic models of cardiac vulnerability should take into account spatial variations of cellular refractoriness. Several new qualitative and quantitative aspects of the VP were revealed, and the modulation of the VP by NaLOF differed significantly in heterogeneous and homogeneous models.     

Anodal block: can this occur during routine nerve conduction studies?

The median nerves of five normal subjects were electrically excited at the wrist with fine-tipped stimulating electrodes in a bipolar fashion. Compound sensory nerve action potentials (CSNAPs) were recorded from the index finger and compound muscle action potentials (CMAPs) from the thenar muscles. Both the cathode and the anode were positioned over the length of the nerve. Recordings were performed with different cathode-to-anode distances of 5, 10, 20, and in some cases, 30 mm. Just supramaximal CSNAPs and CMAPs were obtained initially with the cathode situated distal to the anode and then with the stimulus polarity reversed. There were no significant differences in the amplitude, duration, and morphology of the CSNAPs or CMAPs that were recorded by using different stimulus polarities. There was a consistent increase in the onset latency of the responses when the stimulus polarity was reversed (cathode located proximal to anode). This increase in latency was proportionate to the increase in distance from the cathode to the recording electrode. The effect of anodal block could not be observed from the above experiment.     

Selective stimulation of intrapulpal nerve of rat lower incisor using a bipolar electrode method

The purpose of this study is to determine how reliable the stimulus condition is for selective stimulation of rat lower incisor tooth pulp using a bipolar electrode. In the rat lower incisor, two components were distinguished in the compound action potential, recorded from the inferior alveolar nerve, whose conduction velocities were both in the Aδ-range when only the intrapulpal nerve was stimulated. On increasing the stimulus intensity, the fast component of the compound action potential, which disappeared after local anesthesia was applied to the periodontal tissue, began to reappear, indicating that current spread occurred outside the pulp. The most adequate stimulus conditions for selective intrapulpal nerve stimulation were: (1) interpolar distance of the bipolar electrode: 2 mm, (2) depth of the insertion of the electrode: 20 mm from the tip of the incisor, (3) stimulus pulse duration: 0.1 msec. Under these conditions, rectangular constant current pulses with the intensity of about 50 to 550 μA excited only the intrapulpal nerve. These results suggest that the rat lower incisor may be usefully employed for physiological or behavioral studies of nociceptive mechanisms.     

Effect of subcutaneous fat thickness and surface electrode configuration during neuromuscular electrical stimulation

The effect of subcutaneous fat thickness, electrode size and inter-electrode distance on the minimum stimulus current necessary for fiber excitation was examined in an attempt to improve the efficacy of neuromuscular electrical stimulation (NMES) in obese populations. A three-dimensional finite element model of the human thigh was developed and used to calculate the potential along a myelinated nerve fiber due to NMES. The activating function was used to examine alterations in the excitation of the fiber due to fat thickness, electrode size and inter-electrode distance. The finite element model was coupled to a neural model to examine the stimulus current required for action potential propagation. The stimulus current required to evoke 10% of the maximum M-wave amplitude was measured experimentally. Both experimental and modeling studies indicated that the stimulus current required to reach the threshold for muscle activation increased with fat thickness, electrode size, and inter-electrode distance. However, as fat thickness increased, the threshold for muscle activation became less sensitive to inter-electrode distance and electrode size. These results suggest that by using larger electrodes above regions of high subcutaneous fat thickness, the efficacy of NMES could be maintained while reducing the current density at the skin and the associated subject discomfort.     

Electrophysiological basis of mono-phasic action potential recordings

Monophasic action potentials (MAPs) have been recorded for over a century, however, the exact mechanism responsible for their genesis has yet to be elucidated fully. The goal of the paper is to examine the physical basis of MAP recordings. MAP recordings are simulated by modelling a three-dimensional block of cardiac tissue. The effect of the MAP electrode is modelled by introducing a large, non-specific leakage conductance to the small region under the electrode. From the spread of the electrical activity, the equivalent extracellular current flow can be efficiently determined. These computed current sources are then input into a boundary element model of the tissue to determine the surface potentials. Finally, differences in surface potentials are used to compute waveforms that closely resemble MAP recordings. By varying model parameters, the mechanisms responsible for the MAP are determined, and a theory is put forward that can account for all observations. It is hypothesised that the leakage current causes the formation of a double-layer potential with a strength equal to the difference in transmembrane voltage between the regions under the electrode and those outside the electrode, leading to a recorded potential that mimics the transmembrane voltage outside the electrode region, although offset. Based on experimental MAP recordings, an equivalent leakage channel with a conductance of 0.1 mS cm-2 and a reversal potential of -43 mV is introduced by the electrode.     

外部电场作用下的视神经纤维兴奋性的仿真研究

基于刺入式电极的视神经视觉假体,为盲人的视觉修复提供了新的可能性。为了对该视神经假体的电刺激策略和微电极设计提供理论支持,基于真实的电极结构,在COMSOL软件中建立刺入式微电极的外部电场仿真模型,并将其与利用NEURNO软件实现的神经纤维双层电缆模型结合,系统地研究电极与视神经纤维的相对位置、电刺激脉冲宽度以及电极几何结构的改变对视神经纤维兴奋阈值的影响。不同电极位置、刺激脉宽刺激下阈值变化规律的仿真结果,与以往报道的动物实验和仿真实验结果相符,证明了所建模型的有效性。 根据仿真结果,对刺入式视神经假体中刺激脉宽的选择和电极几何结构的设计,建议如下：窄脉宽刺激有利于降低能量消耗;电极锥度的设计要在满足电极力学特性及易于植入视神经的基础上,尽可能地减小,以降低纤维兴奋的阈值;电极的暴露面积越小,纤维兴奋所需的电流阈值越低,但电荷密度阈值越高;较低的电流阈值有利于减少能量消耗,但过高的电荷密度阈值却容易造成组织损伤,因此电极暴露面积的设计需要在耗能与安全性之间进行综合考虑。电极绝缘层厚度的改变对视神经纤维的兴奋阈值没有明显的影响,但从电极插入的难易考虑,应尽可能减小绝缘层厚度。以上结果对人体其他部位神经纤维的电刺激同样具有参考价值     

Recruitment properties of monopolar and bipolar epimysial electrodes

Muscle force was studied as a function of stimulus parameters, epimysial electrode position relative to nerve supply, and muscle length to provide insight into the properties of motor prostheses that employ epimysial electrodes. The results of the acute experiments indicated that the dependence of recruitment (force versus stimulus amplitude) on muscle length was minimal for a monopolar electrode positioned close to nerve entrance or 5 mm proximal to the motor point. The selectivity of stimulation (minimal activation of adjacent muscles) was best, and the recruitment rate the highest, for an electrode placed close to the nerve entrance. A bipolar pair of electrodes placed on the superficial surface of the muscle opposite to the nerve entrance gave better selectivity than the monopolar electrode at the low end of the recruitment range, and poorer selectivity at the high end. This electrode configuration required greater stimulus currents and exhibited a lower recruitment gain than was obtained for a monopolar electrode in the same position. Examination of tissue surrounding the electrode 30 days after implantation showed that the fibrous tissue encapsulating the electrode had been incorporated into the fascial layer. Slightly larger dependence on muscle length and lower selectivity of stimulation were measured after encapsulation than were measured in the acute experiments. Supported by the NIH-NINCDS Neural Prostheses Program, contract number N01-NS-0-2330 and the Swiss National Science Foundation, grant number 82.722.0.79.     

Membrane capacity of the cardiac Purkinje fibre

1. The basis for the relatively high membrane capacitance of the cardiac Purkinje fibre has been investigated.2. The capacitance measured by analysis of the cable response to a current step (square wave) was compared in the same fibres to the capacitance calculated from the foot of the propagated action potential. The square wave value for capacitance was 12.8 +/- 1.3 muF/cm(2) and that from the foot of the action potential, 2.4 +/- 0.5 muF/cm(2).3. The capacitative filling at the beginning of a voltage clamp in short Purkinje fibres was measured. The current-time course deviated from that predicted by a model membrane containing resistance and capacitance in parallel.4. The results obtained by both methods are consistent with two components to the membrane capacitance, with part in parallel with the membrane resistance (2.4 muF/cm(2)) and part (7 muF/cm(2)) in series with a resistor (300 Omega cm(2)).5. The value of the series resistor could be increased by decreasing the conductivity of the extracellular fluid.6. The possible anatomical basis for these findings is discussed.7. Implications of this model on the shape of the Purkinje fibre action potential and on the electrical triggering of contraction are considered.     

Electrophysiological basis of mono-phasic action potential recordings

Monophasic action potentials (MAPs)_have been recorded for over a century, however, the exact mechanism responsible for their genesis has yet to be elucidated fully. The goal of the paper is to examine the physical basis of MAP recordings. MAP recordings are simulated by modelling a three-dimensional block of cardiac tissue. The effect of the MAP electrode is modelled by introducing a large, non-specific leakage conductance to the small region under the electrode. From the spread of the electrical activity, the equivalent extracellular current flow can be efficiently determined. These computed current sources are then input into a boundary element model of the tissue to determine the surface potentials. Finally, differences in surface potentials are used to compute waveforms that closely resemble MAP recordings. By varying model parameters, the mechanisms responsible for the MAP are determined, and a theory is put forward that can account for all observations. It is hypothesised that the leakage current causes the formation of a double-layer potential with a strength equal to the difference in transmembrane voltage between the regions under the electrode and those outside the electrode, leading to a recorded potential that mimics the transmembrane voltage outside the electrode region, although offset. Based on experimental MAP recordings, an equivalent leakage channel with a conductance of 0.1 mS cm⁻² and a reversal potential of −43 mV is introduced by the electrode.     

Whole heart action potential duration restitution properties in cardiac patients: a combined clinical and modelling study

Steep action potential duration (APD) restitution has been shown to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined clinical electrophysiology and computer modelling study to: (1) determine global APD restitution properties in cardiac patients; and (2) examine the interaction of the observed APD restitution with known arrhythmia mechanisms. In 14 patients aged 52-85 years undergoing routine cardiac surgery, 256 electrode epicardial mapping was performed. Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the entire ventricular surface. Mono-exponential restitution curves were constructed for each electrode site using a standard S1-S2 pacing protocol. The median maximum restitution slope was 0.91, with 27% of all electrode sites with slopes<0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. Eleven per cent of restitution curves maintained slope>1 over a range of diastolic intervals of at least 30 ms; and 0.3% for at least 50 ms. Activation-recovery interval restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. We used a simplified computer model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to, and stability of re-entry. Our model showed that heterogeneity of restitution can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Global epicardial mapping in humans showed that APD restitution slopes were organized into regions of shallow and steep slopes. This heterogeneous organization of restitution may provide a substrate for arrhythmia.     

Cutaneous stimulation evokes long-lasting excitation of spinal interneurons in the turtle

1. We demonstrated multisecond increases in the excitability of the rostral-scratch reflex in the turtle by electrically stimulating the shell at sites within the rostral-scratch receptive field. To examine the cellular mechanisms for these multisecond increases in scratch excitability, we recorded from single cutaneous afferents and sensory interneurons that responded to stimulation of the shell within the rostral-scratch receptive field. A single segment of the midbody spinal cord (D4, the 4th postcervical segment) was isolated in situ by transecting the spinal cord at the segment's anterior and posterior borders. The isolated segment was left attached to its peripheral nerve that innervates part of the rostral-scratch receptive field. A microsuction electrode (4-5 microns ID) was used to record extracellularly from the descending axons of cutaneous afferents and interneurons in the spinal white matter at the posterior end of the D4 segment. 2. The turtle shell is innervated by slowly and rapidly adapting cutaneous afferents. All cutaneous afferents responded to a single electrical stimulus to the shell with a single action potential. Maintained mechanical stimulation applied to the receptive field of some slowly adapting afferents produced several seconds of afterdischarge at stimulus offset. We refer to the cutaneous afferent afterdischarge caused by mechanical stimulation of the shell as "peripheral afterdischarge." 3. Within the D4 spinal segment there were some interneurons that responded to a brief mechanical stimulus within their receptive fields on the shell with short afterdischarge and others that responded with long afterdischarge. Short-afterdischarge interneurons responded to a single electrical pulse to a site in their receptive fields either with a brief train of action potentials or with a single action potential. Long-afterdischarge interneurons responded to a single electrical shell stimulus with up to 30 s of afterdischarge. Long-afterdischarge interneurons also exhibited strong temporal summation in response to a pair of electrical shell stimuli delivered up to several seconds apart. Because all cutaneous afferents responded to an electrical shell stimulus with a single action potential, we conclude that electrically evoked afterdischarge in interneurons was produced by neural mechanisms in the spinal cord; we refer to this type of afterdischarge as "central afterdischarge." 4. These results demonstrate that neural mechanisms for long-lasting excitability changes in response to cutaneous stimulation reside in a single segment of the spinal cord. Cutaneous interneurons with long afterdischarge may serve as cellular loci for multise     

Responses of hair cells in the statocyst of Hermissenda.

Responses to mechanical stimulation were recorded from hair cells in the statocyst of Hermissenda crassicornis. The response to a brief stimulus is a depolarizing wave which reaches peak in about 25 msec and decays slowly. 2. Hyperpolarization by extrinsic currents increases the amplitude of the response; depolarization decreases it and eventually reverses its polarity. It is inferred from these results that the primary outcome of the transduction process is an increase of membrane conductance and that the voltage change (generator potential) follows as a secondary event. 3. The features of the conductance change were reconstructed from the time course of the generator potential and the passive properties of the membrane. It was found that the increase of membrane conductance develops slowly and is roughly proportional to the energy delivered by the stimulus. 4. The time course of the conductance change required to reproduce the generator potential is similar to the output of a model involving a sequence of transformations. 5. The generator potential is sensitive to temperature, becoming faster as temperature is raised. This effect is reproduced by the model if the transition rates are assumed to be temperature-dependent, with a Q10 of about 2. 6. It is concluded that a chain of temperature-sensitive processes is interposed between the stimulus and the increase of membrane conductance.     

Modelling motor cortex stimulation for chronic pain control: Electrical potential field, activating functions and responses of simple nerve fibre models

This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulationinnduced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode.     

An equation describing spread of membrane potential changes in a short segment of blood vessel.

The spread of membrane potential changes throughout certain cells and tissues plays an important role in their physiology. The attenuation of such changes in any tissue is usually characterized by the cable length constant lambda, which can be determined experimentally if the equations describing membrane potential spread in the tissue are known. Here we derive an equation describing spread of membrane potential changes in a short cable, which is an appropriate model for short segments of blood vessels. This equation is more general than those already published in that the positions of both the current source that gives rise to a potential change, and the point at which the change is measured, can be anywhere along the cable.     

Computational analysis of action potential initiation in mitral cell soma and dendrites based on dual patch recordings

In olfactory mitral cells, dual patch recordings show that the site of action potential initiation can shift between soma and distal primary dendrite and that the shift is dependent on the location and strength of electrode current injection. We have analyzed the mechanisms underlying this shift, using a model of the mitral cell that takes advantage of the constraints available from the two recording sites. Starting with homogeneous Hodgkin-Huxley-like Na(+)-K(+) channel distribution in the soma-dendritic region and much higher sodium channel density in the axonal region, the model's channel kinetics and density were adjusted by a fitting algorithm so that the model response was virtually identical to the experimental data. The combination of loading effects and much higher sodium channel density in the axon relative to the soma-dendritic region results in significantly lower "voltage threshold" for action potential initiation in the axon; the axon therefore fires first unless the voltage gradient in the primary dendrite is steep enough for it to reach its higher threshold. The results thus provide a quantitative explanation for the stimulus strength and position dependence of the site of action potential initiation in the mitral cell.     

Low-threshold Ca2+ channels mediate induction of long-term potentiation in kitten visual cortex.

1. The induction mechanism of long-term potentiation (LTP) in developing visual cortex was studied by recording intracellular responses from layer III-IV cells in slice preparations of kitten visual cortex at 30-40 days after birth. 2. Strong stimulation of white matter produced a late depolarizing response after an orthodromic action potential. This depolarizing response was abolished by membrane depolarization or hyperpolarization caused by current injection through the recording electrode. In addition, this response was reduced by bath application of a low concentration (100 microM) of Ni2+ without any changes in the rising slope of the excitatory postsynaptic potential (EPSP) or orthodromic action potential. This suggests that this response is mediated by low-threshold Ca2+ channels (LTCs). 3. The involvement of LTCs in the induction of LTP was tested. White matter was stimulated at 2 Hz for 15 min as a conditioning stimulus to induce LTP, and the resultant changes in EPSPs were tested by low-frequency (0.1 Hz) stimulation of white matter. Conditioning stimulation produced a large N-methyl-D-aspartate (NMDA) receptor-mediated depolarizing response in these cells, which obscured the presence of the late depoliarzation. Therefore the test was conducted in a solution containing an NMDA antagonist 2-amino-5-phosphonovalerate (APV). 4. Weak conditioning stimulation, which evoked no LTC responses, never induced LTP; whereas strong conditioning stimulation, which evoked LTC responses, always induced LTP. Strong conditioning stimulation failed to induce LTP when LTC responses were prevented either by membrane depolarization or hyperpolarization or by a bath application of 100 microM Ni2+. 5. In a solution without APV, the application of Ni2+ also prevented the induction of LTP. 6. When cells were impaled by an electrode containing a Ca2+ chelator 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), LTP was never induced, even though LTC responses were evoked by conditioning stimulation. These results indicate that Ca2+ influx into postsynaptic cells through LTCs induces the LTP. 7. The responses mediated by LTCs, which were evoked by the injection of current pulses into the cells, were maximum at the critical period of visual cortical plasticity, suggesting that LTCs in postsynaptic cells regulate the plastic changes in developing visual cortex.