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Voltage threshold and excitability among variously sized cat hindlimb motoneurons.

Intracellular recording has been performed to examine whether any differences in apparent initial-segment voltage threshold exist between types F and S cat triceps surae motoneurons. Voltage threshold was estimated using orthodromic action potentials initiated by large, monosynaptic excitatory postsynaptic potentials (EPSPs) evoked by dorsal root stimulation. No significant differences in voltage threshold could be detected between types F and S motoneurons. Further, voltage thresholds did not covary with motoneuron input resistance, afterhyperpolarization duration, or the twitch contraction time of functionally isolated muscle units. Significant positive correlations were observed between voltage threshold and the motoneuron resting potential. Utilizing a compartmental neuron model, a theoretical analysis has been performed that examines the influence of specific passive membrane properties on current threshold for action potentials initiated by large, monosynaptic EPSPs. This analysis indicates that total membrane capacitance will be the primary determinant of these thresholds. Further analysis of available data suggests that active membrane properties will play a minimal role in setting these thresholds. Since specific membrane capacitance is likely to be similar among cat motoneurons, it is concluded that only size or surface area-related current threshold differences will exist among these cells for activation with brief currents such as those underlying large EPSPs. For motoneurons thus activated, it is suggested that variations in the excitatory/inhibitory balance or density of synaptic input would be the major mechanisms for producing differential recruitment thresholds among the motoneuron population. Other available evidence is discussed that indicates that factors intrinsic to the motoneurons themselves will contribute to the setting of functional recruitment thresholds for activation with longer duration currents.

Action Potentials↗

The effect of axotomy on posttetanic potentiation of group Ia synapses in the cat.

Posttetanic potentiation (PTP) of composite Ia excitatory postsynaptic potentials (EPSPs) has been studied in normal cat alpha-motoneurons and in motoneurons axotomized 2-3 wk earlier by ventral root section. The maximal amount of PTP of EPSP amplitude (expressed relative to unpotentiated amplitude) was considerably less in the axotomized population compared with the normal population. The decrease in PTP provoked by axotomy occurs in association with a postaxotomy increase of input resistance, the net effect being that PTP in axotomized cells was much the same as that observed by others in normal motoneurons possessing similarly high input resistance. In agreement with previous results, EPSP peak amplitudes were decreased after axotomy. This decrease seemed to be largely related to an absence of the largest EPSPs, since otherwise the EPSP distributions of normal and axotomized motoneurons showed considerable overlap. It is suggested that the observed decrease in PTP after axotomy is related to a change in synaptic release properties and not secondary to changes in the electrical properties of motoneurons. A previous analysis has suggested that axotomy causes an alteration of the distribution of passive electrical properties among motoneurons such that axotomized cells resemble normal high-resistance motoneurons. The present results suggest that axotomy may affect the distribution of Ia synaptic release properties in a similar manner, since PTP in axotomized motoneurons resembles that observed in normal high-resistance motoneurons.

Animals↗

Laminar distribution of neuronal membrane properties in neocortex of normal and reeler mouse.

1. Reeler is an autosomal recessive mutation of mice that alters neuronal migration during development, yielding a general inversion of the laminae in the neocortex. We recorded in vitro from slices of normal and reeler neocortex to study the influence of neuron position and shape on membrane properties and synaptic responses. 2. The intrinsic firing patterns, action-potential shapes, resting membrane potentials, input resistances, and evoked excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) did not differ between reelers and controls when data were grouped. 3. The depth distribution of intrinsic firing patterns was inverted in the reeler: intrinsically bursting (IB) neurons were found only in layer 5 in the normal mouse, but they were found exclusively in supragranular layers of the reeler cortex. 4. The spatial distribution of synaptic responses in the reeler was also inverted: very prominent IPSPs were characteristic of upper layer neurons in the normal mouse, but in the reeler similar inhibitory responses were observed predominantly in deep infragranular layers. 5. Dye injections in reeler pyramidal neurons revealed atypical morphologies, including distorted apical dendrites and cell inversion. 6. The data imply that cortical neurons develop the membrane and synaptic properties appropriate to their function, despite being malformed and mispositioned.

Animals↗

[The development of the slow potentiation of the population spike of a long-term nonstimulating input in rats in a state of anesthetic sleep].

Changes in synaptic efficacy of the medial perforant pathway were studied after the long-term deprivation of the afferent inputs in hippocampus of rats under chloral hydrate or urethane anesthesia. Evoked field potential population spikes and population excitatory postsynaptic potentials were recorded in the dentate gyrus. The long-term deprivation obtained by cessation of stimulation of the tested input for up to 4 hours resulted in an enhancement (up to 190%, p < 0.01) of the population spike amplitude.

Action Potentials↗

Epileptogenic effects of radiographic contrast agents: experimental study.

Electrical activity in cells directly exposed to water-soluble radiographic contrast agents was investigated by intracellular recordings from neurons of the abdominal ganglia of Aplysia. Measurements of membrane resting potential, membrane conductance, synaptic and action potential configuration, and spontaneous electrical activity were performed. Test solutions included sodium diatrizoate, meglumine iothalamate, metrizamide, and control solutions. Solutions (100 and 200 mOsm) of these agents did not significantly alter resting membrane potential, membrane conductance, action potential frequency or configuration, or excitatory postsynaptic potentials. Inhibitory postsynaptic potentials were suppressed by contrast agents. These results suggest that contrast agents affect at least some neurons by disinhibition.

Action Potentials↗

Alterations in potassium currents may trigger neurodegeneration in murine scrapie.

Conventional electrophysiological intracellular recording techniques were used to test the hypothesis that enhanced calcium entry via voltage-gated calcium channels or the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-channel complex may be a primary pathological mechanism triggering neurodegeneration in scrapie and related diseases. This study was carried out at a time when cell loss is known to occur and when hippocampal pyramidal cells in area CA1 are rendered hyperexcitable following scrapie infection. There was no change to the NMDA receptor-mediated component of the Schäffer collateral evoked excitatory postsynaptic potential (EPSP) or the level of spontaneous firing activity of CA1 cells following addition of the specific NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV, 20 microM), to the perfusate in scrapie-infected mice, indicating that the NMDA receptor-channel complex is not compromised by scrapie. There was also no change seen in the non-NMDA mediated component of the EPSP. The calcium spike of CA1 pyramidal cells was not significantly altered by scrapie infection, indicating that high threshold voltage-gated Ca2+ channel function is not compromised by scrapie. By contrast, cells from scrapie-infected mice fired calcium spikes repetitively and the long, slow AHP, which in control cells inhibited repetitive firing, was absent. Cells from scrapie-infected mice showed more depolarized membrane potentials than controls but this difference in potential was no longer observed after exposure to TEA. These data indicate a loss of TEA-insensitive and TEA-sensitive potassium conductances. We suggest that altered potassium currents rather than increased calcium entry via voltage-sensitive calcium channels or the NMDA receptor complex may be the primary pathological mechanism triggering neurodegeneration in scrapie and related diseases.

2-Amino-5-phosphonovalerate↗

Glutamatergic input governs periodicity and synchronization of bursting activity in oxytocin neurons in hypothalamic organotypic cultures.

During suckling, oxytocin (OT) neurons display a bursting electrical activity, consisting of a brief burst of action potentials which is synchronized throughout the OT neuron population and which periodically occurs just before each milk ejection in the lactating rat. To investigate the basis of such synchronization, we performed simultaneous intracellular recordings from pairs of OT neurons identified retrospectively by intracellular fluorescent labelling and immunocytochemistry in organotypic slice cultures derived from postnatal rat hypothalamus. A spontaneous bursting activity was recorded in 65% of OT neurons; the remaining showed only a slow, irregular activity. Application of OT triggered bursts in nonbursting neurons and accelerated bursting activity in spontaneously bursting cells. These cultures included rare vasopressinergic neurons showing no bursting activity and no reaction to OT. Bursts occurred simultaneously in all pairs of bursting OT neurons but, as in vivo, there were differences in burst onset, amplitude and duration. Coordination of firing was not due to electrotonic coupling because depolarizing one neuron in a pair had no effect on the membrane potential of its partner and halothane and proprionate did not desynchronize activity. On the other hand, bursting activity was superimposed on volleys of excitatory postsynaptic potentials (EPSPs) which occurred simultaneously in pairs of neurons. EPSPs, and consequently action potentials, were reversibly blocked by the non-NMDA glutamatergic receptor antagonist CNQX. Taken together, these data, obtained from organotypic cultures, strongly suggest that a local hypothalamic network governs synchronization of bursting firing in OT neurons through synchronous afferent volleys of EPSPs originating from intrahypothalamic glutamatergic inputs.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Stimulation of adenosine A1 and A2A receptors by AMP in the submucosal plexus of guinea pig small intestine.

Actions of adenosine 5'-monophosphate (AMP) on electrical and synaptic behavior of submucosal neurons in guinea pig small intestine were studied with "sharp" intracellular microelectrodes. Application of AMP (0.3-100 microM) evoked slowly activating depolarizing responses associated with increased excitability in 80.5% of the neurons. The responses were concentration dependent with an EC(50) of 3.5 +/- 0.5 microM. They were abolished by the adenosine A(2A) receptor antagonist ZM-241385 but not by pyridoxal-phosphate-6-azophenyl-2,4-disulfonic acid, trinitrophenyl-ATP, 8-cyclopentyl-1,3-dimethylxanthine, suramin, or MRS-12201220. The AMP-evoked responses were insensitive to AACOCF3 or ryanodine. They were reduced significantly by 1) U-73122, which is a phospholipase C inhibitor; 2) cyclopiazonic acid, which blocks the Ca(2+) pump in intraneuronal membranes; and 3) 2-aminoethoxy-diphenylborane, which is an inositol (1,4,5)-trisphosphate receptor antagonist. Inhibitors of PKC or calmodulin-dependent protein kinase also suppressed the AMP-evoked excitatory responses. Exposure to AMP suppressed fast nicotinic ionotropic postsynaptic potentials, slow metabotropic excitatory postsynaptic potentials, and slow noradrenergic inhibitory postsynaptic potentials in the submucosal plexus. Inhibition of each form of synaptic transmission reflected action at presynaptic inhibitory adenosine A(1) receptors. Slow excitatory postsynaptic potentials, which were mediated by the release of ATP and stimulation of P2Y(1) purinergic receptors in the submucosal plexus, were not suppressed by AMP. The results suggest an excitatory action of AMP at adenosine A(2A) receptors on neuronal cell bodies and presynaptic inhibitory actions mediated by adenosine A(1) receptors for most forms of neurotransmission in the submucosal plexus, with the exception of slow excitatory purinergic transmission mediated by the P2Y(1) receptor subtype.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Modulation of monosynaptic transmission by presynaptic inhibition during fictive locomotion in the cat.

The effect of multisensory inputs onto the presynaptic inhibitory pathways affecting IA terminals was studied during fictive locomotion in decerebrated cats. The effect was evaluated from changes in amplitude of the monosynaptic excitatory postsynaptic potential (EPSP) measured in lumbosacral motoneurones. Responses were grouped and averaged according to their timing within the step cycle divided into five bins. Presynaptic inhibition was evoked by stimulating group I afferents from the posterior biceps-semitendinosus (PBSt) muscles and one of three cutaneous nerves: superficial peroneal (SP), sural and saphenous. Statistical analysis was applied to compare (1) EPSPs conditioned by PBSt input alone and those conditioned by the combined PBSt and cutaneous inputs, and (2) each bin dividing the step cycle to disclose phase-dependent changes. Results from 19 motoneurones showed that: (1) there was a significant phase-dependent modulation in EPSP amplitude (by 25%) with the maximum usually occurring during the depolarized phase; (2) PBSt alone reduced the EPSP amplitude (by 21%) in 3.2 bins on average; (3) combined PBSt and cutaneous stimuli further modified (up or down) the EPSP amplitude in half the trials but only in one to two bins; and (4) the most efficient cutaneous nerve (SP) usually decreased the PBSt-evoked reduction in EPSP size. Minimal changes in membrane input resistance suggest that the EPSP modifications were mostly due to presynaptic inhibition. Results indicate that muscle afferents can induce an important phase-dependent presynaptic inhibition of monosynaptic transmission and that concomitant activation of cutaneous afferents can alter this inhibition but only for a restricted part of the step cycle.

Action Potentials↗

Cocaine-induced modulation of long-term potentiation in the CA1 region of rat hippocampus.

In order to further characterize the actions of cocaine on synaptic activity in the hippocampus, recordings of field excitatory postsynaptic potentials in the CA1 region of the rat hippocampal slice preparation were used to monitor drug effects on long-term potentiation (LTP) evoked in response to stimulation of the Schaffer collateral pathway. Cocaine had dose-dependent, biphasic effects on the magnitude of LTP at these excitatory synapses in the stratum radiatum ranging from a significant enhancement of LTP at intermediate drug concentrations (5-10 microM), to an inhibition of LTP at a relatively high drug concentration (30 microM). The local anesthetic lidocaine had only inhibitory effects on the induction of LTP at all concentrations examined (10-75 microM), whereas the monoamine transporter antagonists, WIN 35348 (1 microM) or GBR 12935 (5 microM) significantly enhanced the magnitude of LTP. The D(2)-like dopamine receptor antagonist, eticlopride was effective in preventing this action of cocaine, whereas pretreatment with the D(1/5) antagonist, SCH 23390 was ineffective. These results suggest that endogenously released dopamine, in the presence of cocaine (5-10 microM), can act via D(2)-like receptors to significantly increase the magnitude of LTP in the CA1 region of the hippocampus.

Adrenergic beta-Antagonists↗

Long-term facilitation of excitatory synaptic transmission in single motor cortical neurones of the cat produced by repetitive pairing of synaptic potentials and action potentials following intracellular stimulation.

The effects of postsynaptic firing activity on excitatory postsynaptic potentials (EPSPs) were studied in the motor cortex of anaesthetized cats. Postsynaptic firing was induced by 1-5 nA cathodal current pulses via the recording intracellular microelectrode, while EPSPs were elicited by thalamic, callosal, pyramidal tract and somatosensory stimuli. In 102 cells, EPSP-spike stimulus pairs were applied with 0.2-1/sec frequency and 10-100 msec interstimulus intervals. In 42 neurones, reversible facilitation of paired EPSPs appeared lasting from 4 to 47 min. The synaptic facilitation in most cases was accompanied by membrane depolarization and an increase in input resistance. The effectiveness of current induced action potentials upon test EPSPs provided evidence for the postsynaptic localization of plastic changes occurring in conditioning experiments.

Action Potentials↗

Physiological properties of late inspiratory neurons and their possible involvement in inspiratory off-switching in cats.

To assess the functional significance of late inspiratory (late-I) neurons in inspiratory off-switching (IOS), membrane potential and discharge properties were examined in vagotomized, decerebrate cats. During spontaneous IOS, late-I neurons displayed large membrane depolarization and associated discharge of action potentials that started in late inspiration, peaked at the end of inspiration, and ended during postinspiration. Depolarization was decreased by iontophoresis of dizocilpine and eliminated by tetrodotoxin. Stimulation of the vagus nerve or the nucleus parabrachialis medialis (NPBM) also evoked depolarization of late-I neurons and IOS. Waves of spontaneous chloride-dependent inhibitory postsynaptic potentials (IPSPs) preceded membrane depolarization during early inspiration and followed during postinspiration and stage 2 expiration of the respiratory cycle. Iontophoresed bicuculline depressed the IPSPs. Intravenous dizocilpine caused a greatly prolonged inspiratory discharge of the phrenic nerve (apneusis) and suppressed late-inspiratory depolarization as well as early-inspiratory IPSPs, resulting in a small constant depolarization throughout the apneusis. NPBM or vagal stimulation after dizocilpine produced small, stimulus-locked excitatory postsynaptic potentials (EPSPs) in late-I neurons. Neurobiotin-labeled late-I neurons revealed immunoreactivity for glutamic acid decarboxylase as well as N-methyl-D-aspartate (NMDA) receptors. These results suggest that late-I neurons are GABAergic inhibitory neurons, while the effects of bicuculline and dizocilpine indicate that they receive periodic waves of GABAergic IPSPs and glutamatergic EPSPs. The data lead to the conclusion that late-I neurons play an important inhibitory role in IOS. NMDA receptors are assumed to augment and/or synchronize late-inspiratory depolarization and discharge of late-I neurons, leading to GABA release and consequently off-switching of bulbar inspiratory neurons and phrenic motoneurons.

Action Potentials↗

Effect of FK960, a putative cognitive enhancer, on synaptic transmission in CA1 neurons of rat hippocampus.

The action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel cognitive enhancer, on excitatory synaptic transmission in the hippocampus was investigated. Excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were recorded intracellularly from CA1 neurons in rat hippocampus using the "blind patch" variant of whole-cell recording. FK960 (100 nM) significantly increased the amplitude of the EPSP, which was unchanged when changeover was made to control artificial cerebrospinal fluid (aCSF). FK960 had no significant action on membrane potential, input resistance, or the early GABAergic inhibitory postsynaptic current. The decay phase of the excitatory postsynaptic current was not significantly altered by exposure to FK960, indicating that the properties of desensitization and/or deactivation were unchanged and suggesting that the action of FK960 was unlikely to be the result of changes in the properties of the postsynaptic (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors. The quantal content of the EPSP (1/CV(2)) increased after exposure to FK960 but not to control aCSF. Methyllycaconitine or alpha-bungarotoxin blocked the modulatory action of FK960 on the EPSP, and the finding that these alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR) antagonists were effective raises the possibility that FK960 up-regulates the contribution of acetylcholine to synaptic efficacy in the hippocampus. It is concluded that FK960 increases the quantal release of glutamate from Schaffer collateral-commissural nerve terminals in area CA1 of the hippocampus either by changing the ambient level of acetylcholine or by positively modulating the activity of alpha 7nAChRs located on glutamatergic nerve terminals.

Aconitine↗

A postsynaptic G-protein in hippocampal long-term potentiation.

The effects of guanosine triphosphate (GTP)-binding protein (G-protein) blockade on hippocampal LTP at stratum radiatum-CA1 synapses was studied. Bath application of 20 mM lithium chloride (LiCl) inhibited long-term potentiation (LTP) of extracellularly-recorded excitatory postsynaptic potentials (EPSPs). Inclusion of 100 mM LiCl in intracellular recording electrodes was shown to block postsynaptic G-proteins by bath-application of baclofen, an agonist at the G-protein linked gamma-aminobutyric acid (GABAB) receptor. Under normal conditions, GABAB receptor activation causes a hyperpolarization postsynaptically, and a decrease in neurotransmitter release presynaptically. With LiCl in the recording electrodes, the postsynaptically-mediated hyperpolarization was blocked, while the presynaptically-mediated depression of EPSPs was unaffected. With postsynaptic G-proteins blocked in this manner, LTP at these synapses was inhibited. These studies provide evidence for the involvement of a postsynaptic G-protein in LTP of stratum radiatum-CA1 synapses.

Animals↗

Inhibitor of glutamate transport alters synaptic transmission at sensorimotor synapses in Aplysia.

Aplysia sensory neurons possess high-affinity glutamate uptake activity that is regulated by serotonin. To gain insight into the physiological role of glutamate uptake in sensory neurons, we examined whether blockade of glutamate transport altered synaptic transmission. We also examined whether glutamate transport affected homosynaptic depression and posttetanic potentiation (PTP). In the presence of DL-threo-beta-hydroxyaspartic acid (THA), previously shown to block glutamate uptake in Aplysia, the duration of unitary excitatory postsynaptic potentials (EPSPs) was significantly increased and their amplitude was significantly reduced. Similar effects were observed in the properties of summated EPSPs. However, no effect on the induction of homosynaptic depression or PTP was observed. Although it is unclear whether THA exerted its effect by modulating neuronal and/or glial mechanisms, at least one target of THA was neuronal, as the duration of unitary EPSPs measured in cultured sensorimotor synapses was also increased in the presence of THA. These results support the hypotheses that glutamate is the transmitter released by the sensory neurons and that glutamate transport plays an important role in regulating features of synaptic transmission in Aplysia.

Action Potentials↗

Kindling induces transient fast inhibition in the dentate gyrus--CA3 projection.

The granule cells of the dentate gyrus (DG) send a strong glutamatergic projection, the mossy fibre tract, toward the hippocampal CA3 field, where it excites pyramidal cells and neighbouring inhibitory interneurons. Despite their excitatory nature, granule cells contain small amounts of GAD (glutamate decarboxylase), the main synthetic enzyme for the inhibitory transmitter GABA. Chronic temporal lobe epilepsy results in transient upregulation of GAD and GABA in granule cells, giving rise to the speculation that following overexcitation, mossy fibres exert an inhibitory effect by release of GABA. We therefore stimulated the DG and recorded synaptic potentials from CA3 pyramidal cells in brain slices from kindled and control rats. In both preparations, DG stimulation caused excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequences. These potentials could be completely blocked by glutamate receptor antagonists in control rats, while in the kindled rats, a bicuculline-sensitive fast IPSP remained, with an onset latency similar to that of the control EPSP. Interestingly, this IPSP disappeared 1 month after the last seizure. When synaptic responses were evoked by high-frequency stimulation, EPSPs in normal rats readily summate to evoke action potentials. In slices from kindled rats, a summation of IPSPs overrides that of the EPSPs and reduces the probability of evoking action potentials. Our data show for the first time that kindling induces functionally relevant activity-dependent expression of fast inhibition onto pyramidal cells, coming from the DG, that can limit CA3 excitation in a frequency-dependent manner.

2-Amino-5-phosphonovalerate↗

Optical imaging of long-lasting depolarization on burst stimulation in area CA1 of rat hippocampal slices.

Postsynaptic depolarization of dendrites paired with spike generation at the soma is considered to be a central mechanism of long-term potentiation (LTP) induction and a prime example of a Hebbian synapse. This pairing, however, has never been actually demonstrated on tetanic stimulation. Optical imaging of neural activity with a voltage-sensitive dye (VSD) is one potentially suitable method for examining this pairing. It is possible with optical recording to examine simultaneously the excitation of postsynaptic neurons at multiple sites. Thus the pairing of spike generation at the soma and dendritic depolarization can be examined with population level optical recording in highly laminar structures such as the hippocampal slice preparation. For example, one can correlate the optical signals obtained from cell layers with the activity of the soma, and, similarly, optical signals from stratum radiatum can be correlated with the activity of the apical dendrite, even though one cannot calibrate the optical signals in terms of actual membrane potential. Using the VSD aminonaphthylethenylpyridinium in rat hippocampal slices, we aimed to examine the pairing. Standard tetanic stimulation (100 Hz, 1 s) that elicited LTP in the field excitatory postsynaptic potential (fEPSP) resulted in a long-lasting depolarizing optical signal (about 2 s) that spread progressively along the known input pathway of CA1. The time course of this long-lasting depolarization was similar to that recorded intracellularly and to that reflected in the fEPSP. The long-lasting depolarization was insensitive to D,L-2-amino-5-phosphonovaleric acid (D,L-APV, 50 microM), but D,L-APV inhibited the induction of LTP; this allowed us to increase the signal-to-noise ratio of the optical signal by averaging several trials. Using this improved optical signal, we confirmed that postsynaptic cells practically "missed" spikes during tetanic stimulation in most parts of CA1, which had been suggested in the intracellular recordings. Intracellular recordings revealed a 23% reduction in input resistance, which might explain the failed spike generation at the soma via shunting. A steep spatial convergence of the depolarization along the transverse axis of area CA1 was observed. In contrast to the response resulting from a standard 100-Hz tetanus, broader activation, and paired depolarization with somatic spikes was observed on theta-burst stimulation. Overall we concluded that postsynaptic spike generation, at least in synchronous form, has less effect on LTP induction with standard tetanic stimulation, while theta-burst tetanic stimulation can elicit pairing of dendritic depolarization and somatic discharge.

Action Potentials↗

Retigabine strongly reduces repetitive firing in rat entorhinal cortex.

Retigabine (D-23129) [N-(2-amino-4-(4-fluorobenzylamino)phenyl) carbamic acid ethyl ester] is a novel antiepileptic drug. The compound was shown to possess anticonvulsant properties both in vivo and in vitro. We investigated the effects of retigabine on neurones in the rat medial entorhinal cortex using conventional intracellular recordings in combined hippocampal-entorhinal cortex slices. Retigabine strongly reduced the number of action potentials elicited by 1 s long depolarising current injections. Both the amplitudes of monosynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) and the amplitudes of excitatory postsynaptic potentials (EPSPs) remained unaffected. The drug increased outward rectification and induced a membrane-potential hyperpolarisation in most of the tested neurones. The findings suggest that retigabine exerts its anticonvulsant effects by activation of a K(+)conductance, however it cannot be excluded from our experiments that other mechanisms may be involved in the effect of retigabine on membrane properties.

Animals↗