Biomedical subjects

B Sutor

Publications and source records attributed to B Sutor.

At least 37 records · Page 2Linked to original sources

PubMed1996

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic denervation potentiates gabaergic inhibition in the mouse neostriatum in vitro.

Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease, we investigated the long-term effects of dopaminergic denervation on synaptic transmission in an in vitro slice preparation of the mouse neostriatum. In control mice, electrical stimulation elicited an antidromic potential (N1) followed by a synaptically mediated field potential (N2). In many slices, a third component (N3) was observed. Determination of the maximum stimulus intensities unveiled that in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreated animals, the stimulus strength necessary to evoke a maximum N2 response was significantly higher compared to control mice. Furthermore, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreatment led to a less frequent appearance and/or to a reduction in the amplitude of the N3 component. Application of glutamate receptor agonists and antagonists revealed two additional differences between normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (1) Comparison of the efficacy of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione demonstrated an increase in the inhibitory effect of 6-cyano-7-nitroquinoxaline-2,3-dione in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (2) In normal mice, removal of magnesium ions from the bathing solution invariably led to the appearance of late N-methyl-D-aspartate receptor-dependent synaptic components. There components were only slightly expressed or virtually absent in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. The described differences between the electrophysiological and pharmacological properties of evoked field potentials in slices from normal and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreated mice disappeared following blockade of GABAA receptor-dependent inhibition by bicuculline. In normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice, bicuculline did not influence the amplitude of the N2 component, but invariably unmasked late synaptic components mediated by glutamate receptors. However, the potentiating effect of bicuculline was significantly stronger in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice compared to the controls. In the presence of bicuculline, the frequency of occurrence of the N3 component was identical in both groups. Furthermore, the apparent efficiency of 6-cyano-7-nitroquinoxaline-2,3-dione was no longer different. Application of bicuculline in the absence of magnesium ions resulted in a similar disinhibition of N-methyl-D-aspartate receptor-dependent late components as observed in the controls in the absence of bicuculline. The data demonstrate that chronic dopaminergic denervation reduces glutamate receptor-dependent synaptic excitation in the mouse neostriatum. Since differences between normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice disappear in the presence of bicuculline, we conclude that this reduction in excitability is due to a potentiation of GABAA receptor-dependent inhibition.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1996

Serotonin regulates gap junction coupling in the developing rat somatosensory cortex.

To further elucidate the role of the neuromodulatory transmitter serotonin (5-HT) during early postnatal development of the neocortex, we investigated the effects of 5-HT on gap junction coupling in the somatosensory cortex of rats aged between postnatal days 7 and 10. The gap junction-permeable tracer neurobiotin was injected into single neurons via microelectrodes or patch pipettes. Under control conditions, clusters of about 25 tracer-coupled neurons were observed. Serotonin reduced dye-coupling between lamina II/III pyramidal cells in a concentration-dependent and reversible manner. The 1,4,5-inositol triphosphate (IP3) receptor antagonist heparin as well as the protein kinase C inhibitor NPC 15437 suppressed the uncoupling action of 5-HT, suggesting that the serotonergic effect involved IP3 receptor-mediated release of calcium ions from intracellular stores. In contrast, the 5-HT-induced reduction in gap junction coupling was not antagonized by Rp-adenosine-3',5'-cyclic monophosphothionate, an inhibitor of cAMP dependent protein kinase. The uncoupling effect of 5-HT was mimicked by 5-HT2 receptor agonists and antagonized by the 5-HT2 receptor antagonist ritanserin, indicating that 5-HT suppressed gap junction coupling via activation of 5-HT2 class receptors. Our results suggest that the developmental functions of 5-HT not only involve the modulation of chemical synaptic transmission but also include the regulation of the gap junctional communication system during differentiation of the neocortex.

Animals↗

PubMed1996

Steroid-induced depressive psychosis responsive to electroconvulsive therapy.

We report the case of a 15-year-old girl with acute lymphoblastic leukemia who developed a severe steroid-induced depression, which was rapidly responsive to ECT. This report adds to the growing body of literature supporting ECT as a safe and effective treatment of affective and psychotic disorders in children.

Adolescent↗

PubMed1995

Beta-adrenoreceptor activation reduces dye-coupling between immature rat neocortical neurones.

The present study examined the effect of activation of adrenergic receptors by noradrenaline and the beta-receptor selective agonist isoproterenol on dye-coupling between developing lamina II/III pyramidal neurones in rat prefrontal and sensorimotor cortex. To assess dye-coupling neurones were intracellularly injected with neurobiotin. Under control conditions injections performed in slices obtained from neonatal rats (7-10 postnatal days) resulted in clusters of more than 30 tracer-coupled neurones. Preincubation with either isoproterenol or noradrenaline reduced the number of coupled cells by 60-80%. The effect of isoproterenol was suppressed by the beta 1-adrenoreceptor antagonist atenolol. Our results indicate that modulation of gap junction coupling between differentiating neocortical neurones might be one important function of noradrenergic afferents during early postnatal development of the neocortex.

Adrenergic beta-Agonists↗

PubMed1995

Delta, mu and kappa opioid receptor agonists inhibit dopamine overflow in rat neostriatal slices.

The actions of opioid receptor agonists on stimulus evoked dopamine overflow in rat neostriatal slices were investigated using fast cyclic voltammetry. Activation of delta and mu receptors reversibly depressed striatal dopamine efflux induced by intrastriatal stimulation. The inhibitory effect of DADLE (D-Ala2, D-Leu5-enkephalin, delta/mu agonist), DPDPE (D-Pen2,5-enkephalin, delta selective) and DALDA (D-Arg2, Lys4-dermorphin-(1,4)-amide, mu selective), respectively, were concentration dependent and could be blocked by application of receptor subtype selective antagonists. At a concentration of 1 microM, the kappa receptor agonist U-50488H inhibited dopamine overflow. This effect could be partially antagonized by kappa receptor selective antagonists. Prior application of virtually ineffective concentrations (< or = 0.1 microM) of the kappa agonist reduced the efficacy of 1 microM U-50488H suggesting a desensitization of the receptor. Since the stimulus induced dopamine overflow in striatal slices can be attributed solely to the release of dopamine from presynaptic terminals, these experiments demonstrate that delta, mu and kappa opioid receptors exert an inhibitory control on striatal dopamine release via a presynaptic mechanism.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

Dye coupling between pyramidal neurons in developing rat prefrontal and frontal cortex is reduced by protein kinase A activation and dopamine.

During early postnatal development, lamina II/III pyramidal cells in rat neocortex are extensively coupled via gap junctions. The factors regulating gap junction permeability, as well as the mechanisms underlying the developmental uncoupling process are not understood. To investigate the influence of protein kinase A-mediated phosphorylation on dye coupling in the developing neocortex, pyramidal cells in slices of rat frontal and prefrontal cortex were injected intracellularly with the tracer neurobiotin. Control injections revealed clusters of about 30 dye-coupled neurons. Preincubation with forskolin or direct activation of protein kinase A with Sp-cAMPS reduced the number of coupled cells by about 70%. A significant reduction in dye coupling was also observed following incubation with dopamine. Application of receptor selective agonists and antagonists revealed that the uncoupling was mediated by both dopamine D1 and D2 receptors. The protein kinase A inhibitor Rp-cAMPS reduced the effect of dopamine, suggesting that the neurotransmitter regulates gap junction permeability via protein kinase A activation. In the presence of either forskolin, Sp-cAMPS, or dopamine, neurons displayed a significantly higher input resistance compared to control conditions. During the second postnatal week, transient application of forskolin to single neurons reversibly increased input resistance. At later developmental stages when coupling incidence had declined, this action of forskolin was no longer observed. Our data demonstrate a dependence of gap junction permeability on protein kinase A activity and on dopamine receptor activation in developing rat neocortical neurons. These mechanisms may modulate junctional permeability during the period of circuit formation.

Aging↗

PubMed1995

Development of excitatory and inhibitory postsynaptic potentials in the rat neocortex.

The postnatal development of synaptic potentials in the rat neocortex is characterized by the sequential appearance of functional excitatory and inhibitory synapses. Morphological and electrophysiological studies provided evidence that at early stages of development, pyramidal cells are extensively coupled to each other, presumably via gap junctions. Thus, immature neurons are able to communicate through pathways that are not available or only weakly expressed in the mature neocortex. During the very early postnatal period, excitatory synaptic inputs prevail. Excitatory postsynaptic potentials (EPSPs) are characteristically long in duration and show high sensitivity to frequent stimulation. Although spontaneous inhibitory postsynaptic potentials (IPSPs) and mature responses to exogenously applied gamma-aminobutyric acid (GABA) have been described during the first postnatal week, evoked IPSPs do not develop before postnatal day 10 (P10). During the period of maximum synaptogenesis (P11 to P20), GABA-mediated synaptic inhibition develops and pyramidal cells respond to afferent activation with efficient EPSPs and IPSPs. These postsynaptic potentials gradually mature during the late postnatal period. The delayed development of synaptic inhibition in the neocortex simultaneously promotes synaptic plasticity while increasing seizure susceptibility. On the one hand, the functional lack of synaptic inhibition during early stages of development enables a period of enhanced neuronal activity and augmented synaptic plasticity necessary to form proper synaptic connections. On the other hand, the absence of inhibitory control over excitatory processes increases the vulnerability of the developing neocortex to seizure activity during postnatal ontogenesis.

Aging↗

PubMed1994

Cholinergic modulation of dopamine overflow in the rat neostriatum: a fast cyclic voltammetric study in vitro.

Stimulus-evoked dopamine overflow in rat neostriatal slices was determined using fast cyclic voltammetry. The dopamine efflux induced by intrastriatal stimulation increased with stimulus intensity and was found to be enhanced by more than 100% upon application of the dopamine uptake inhibitor nomifensine. The acetylcholine esterase inhibitor eserine concentration-dependently and reversibly depressed stimulus-induced dopamine overflow. This effect was mediated by both, muscarinic and nicotinic cholinergic receptors: the action of eserine was mimicked by cholinergic agonists (muscarine and nicotine) and the effects of these agonists were blocked by muscarinic and nicotinic antagonists (atropine and dihydro-beta-erythroidine). These experiments suggest that endogenous acetylcholine exerts an inhibitory control on stimulus-evoked (i.e. phasic) dopamine overflow in vitro by affecting striatal dopaminergic nerve terminals.

Animals↗

PubMed1994

Spread of epileptiform activity in the immature rat neocortex studied with voltage-sensitive dyes and laser scanning microscopy.

1. Adult rats and rats with a postnatal age of 3-29 days (PN 3-29) were used for the preparation of in vitro slices of the frontal neocortex. Epileptiform activity was induced by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonists bicuculline or picrotoxin. 2. The voltage-sensitive dye RH 414 and a laser scanning microscope were used for multiple-site optical recordings of membrane potential changes associated with epileptiform activity. Optical signals were compared with simultaneously measured extra-cellular field potentials. 3. Optical signals could be reliably recorded for the duration of the experiments (2-4 h). Extracellular recordings of convulsant-induced paroxysmal depolarizing shifts (PDSs) in slices stained with RH 414 were comparable with those obtained in unstained slices. Changes in dye signals in response to reductions in extracellular calcium, addition of tetrodotoxin (TTX), or application of excitatory amino acid receptor antagonists indicate that the fluorescence changes correlate well with established electrophysiological measures of epileptiform activity. 4. In slices from adult animals, dye signals were observed at all recording sites. The response with the shortest latency occurred invariably at the site of stimulation, and activity spread rapidly in both vertical and horizontal directions. Spread was significantly faster in the vertical than in the horizontal direction. 5. Epileptiform activity was absent or only weakly expressed in slices from PN 3-9 animals. Activity was detectable predominantly in upper cortical layers. 6. Dye signals were observed at all measurement points in slices from PN 10-19 animals. In this age group, peak amplitude increased with spread of activity from lower to upper cortical layers. There was no significant difference between the speed of propagation in the vertical and in the horizontal directions. Spontaneous epileptiform activity occurred at a high rate in the PN 10-19 age group, and signals associated with spontaneous epileptiform events were largest in upper layers. 7. In the PN 10-19 age group, optical signals were characterized by the repetitive occurrence of PDS discharges superimposed on a sustained response. The amplitude of the sustained response decreased with increasing distance from the site of stimulation. Analysis of the latencies revealed that the superimposed PDS-like events were generated at multiple sites within the scanning area. Amplitude and rate of rise were largest in slices from PN 10-19 animals. These values declined with ongoing development.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

PubMed1993

Influence of barium on rectification in rat neocortical neurons.

The effect of low concentrations of barium on the membrane properties of rat neocortical neurons was studied in vitro. Potassium currents were examined using single-electrode current- and voltage-clamp techniques. Neurons responded to bath application of barium (10-100 microM) with a membrane depolarization associated with an increase in input resistance. Under voltage clamp conditions, an inward shift in holding current was observed. The effects of barium were rapidly reversible upon washing and persisted in the presence of TTX. The equilibrium potential for the barium-induced inward current was near -110 mV, suggesting that barium inhibited a tonically active potassium conductance. Measurements of current-voltage relationships indicated an inward rectification of this conductance between -50 and -130 mV. These results provide strong evidence that barium blocks a persistent potassium 'leak' current in neocortical neurons that contributes to the resting potential of these cells.

Animals↗

PubMed1993

Disinhibition of hippocampal CA3 neurons induced by suppression of an adenosine A1 receptor-mediated inhibitory tonus: pre- and postsynaptic components.

Intracellular recordings were performed on hippocampal CA3 neurons in vitro to investigate the inhibitory tonus generated by endogenously produced adenosine in this brain region. Bath application of the highly selective adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine at concentrations up to 100 nM induced both spontaneous and stimulus-evoked epileptiform burst discharges. Once induced, the 1,3-dipropyl-8-cyclopentylxanthine-evoked epileptiform activity was apparently irreversible even after prolonged superfusion with drug-free solution. The blockade of glutamatergic excitatory synaptic transmission by preincubation of the slices with the amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), but not with the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid (50 microM), prevented the induction of epileptiform activity by 1,3-dipropyl-8-cyclopentylxanthine. The generation of the burst discharges was independent of the membrane potential, and the amplitude of the slow component of the paroxysmal depolarization shift increased with hyperpolarization, indicating that the 1,3-dipropyl-8-cyclopentylxanthine-induced bursts were synaptically mediated events. Recordings from tetrodotoxin-treated CA3 neurons revealed a strong postsynaptic component of endogenous adenosinergic inhibition. Both 1,3-dipropyl-8-cyclopentylxanthine and the adenosine-degrading enzyme adenosine deaminase produced an apparently irreversible depolarization of the membrane potential by about 20 mV. Sometimes, this depolarization attained the threshold for the generation of putative calcium spikes, but no potential changes resembling paroxysmal depolarization shift-like events were observed. At the concentrations used in electrophysiological experiments (30-100 nM), 1,3-dipropyl-8-cyclopentylxanthine displayed only a negligible inhibitory action on total cyclic nucleotide phosphodiesterase activity measured by means of a radiochemical assay in a homogenate of the rat cerebral cortex. Furthermore, even high concentrations of the selective phosphodiesterase inhibitor rolipram (10 microM), which displays no affinity to adenosine receptors, did not mimic the electrophysiological actions of 1,3-dipropyl-8-cyclopentylxanthine, thus excluding the possibility that the effects of the A1 receptor antagonist on neuronal discharge behavior can be ascribed to an inhibition of phosphodiesterases. The present data demonstrate that endogenously released adenosine exerts a vigorous control on the excitability of hippocampal CA3 neurons on both the pre- and postsynaptic sites. The long-lasting disinhibition following a transient suppression of adenosinergic inhibition strongly suggests that, besides its well-known short-term effects on neuronal activity, adenosine might also contribute to the long-term control of hippocampal excitability.

Animals↗

PubMed1993

Compliance changes in venous insufficiency.

In 37 patients (69 limbs) referred to Mayo Clinic's Vascular Center for possible venous valvular insufficiency in the lower limb, calf muscle pump function, calf compliance, and venous refilling times were measured by strain gauge plethysmography techniques. Patient limbs were separated into four categories based on 90% refilling time (T90) following fifteen deep knee bends: normal (n = 16), mild/moderate (n = 28), severe (n = 16), and edema of nonvenous origin (n = 9). Pump function was assessed in actual pumping volumes (mL) and in percent pumping volumes (mL/100 mL), and was reduced in all noncontrol categories. Calf compliance was assessed in actual volume change (mL/mmHg) and in percent volume change (mL/100 mL/mmHg) and was increased in the severe reflux category. Ten study patients had 1 normal category limb and 1 reflux category limb. Paired analysis of these limbs showed pump function to be decreased and calf compliance to be increased in the diseased group limbs.

Compliance↗

PubMed1990

Ascorbic acid: a useful reductant to avoid oxidation of catecholamines in electrophysiological experiments in vitro?

The actions of the reductant ascorbic acid on rat neocortical neurons in vitro was investigated by means of intracellular recordings. At a concentration (500 microM), which reduced the magnitude of dopamine degradation in oxygen-saturated saline solutions by about 50%, ascorbic acid reversibly depressed synaptic potentials and enhanced direct excitability of cortical neurons. The latter effect was not reversible within the observation period. Ascorbic acid did not alter membrane potential and input resistance of the neurons. On the basis of our results we conclude that ascorbic acid is not a useful reductant to avoid oxidation of catecholamines in oxygen-saturated solutions used in electrophysiological experiments in vitro.

Animals↗

PubMed1990

Presynaptic M1 muscarinic cholinoceptors mediate inhibition of excitatory synaptic transmission in the hippocampus in vitro.

The effects of the cholinoceptor agonist, carbachol (CCh), were examined in the rat hippocampal slice preparation. Intracellular recordings from CA1 pyramidal neurones revealed that CCh (1-3 microM) inhibited excitatory postsynaptic responses evoked by stimulation of the Schaffer collateral/commissural pathway while, at the same time, direct excitability was enhanced. Extracellularly, CCh produced a concentration-dependent reduction of the amplitude of the field excitatory postsynaptic potential (field EPSP) recorded in the CA1 apical dendritic region. The muscarinic receptor antagonist, pirenzepine, competitively antagonized the effects of CCh on the field EPSP with a pA2 of 7.4. These results confirm earlier reports of a presynaptic inhibitory action of CCh in the hippocampal CA1 region and provide strong evidence that this effect is mediated by muscarinic receptors of the M1 subtype.

Action Potentials↗

PubMed1990

The low KM-phosphodiesterase inhibitor denbufylline enhances neuronal excitability in guinea pig hippocampus in vitro.

The actions of the phosphodiesterase inhibitor denbufylline on the excitability of hippocampal neurons were investigated by means of extracellular and intracellular recordings. Denbufylline, which has been shown to selectively inhibit a low KM, Ca2+/calmodulin-independent phosphodiesterase isozyme, concentration-dependently increased the amplitude of the extracellularly recorded CA1 population spike evoked by electrical stimulation of the Schaffer collateral/commissural pathway. Concentration-response-curves yielded an EC50 for denbufylline of 0.76 microM. In comparison, the non-selective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) also produced an increase in the amplitude of the population spike. From the concentration-response-curve, which was steeper than that of denbufylline, an EC50 for IBMX of 1.04 microM was obtained. However, despite their similar EC50 values, denbufylline was found to be significantly more potent at lower concentrations (less than or equal to 300 nM) than IBMX. Intracellular recordings from CA1 pyramidal cells revealed postsynaptic actions of denbufylline (300 nM) as indicated by a small drug-induced depolarization (2-5 mV) associated with an increase in membrane input resistance by 10-20%. In addition, denbufylline blocked the accommodation of trains of action potentials evoked by the injection of depolarizing current pulses. The results suggest i) that accumulation of adenosine-3',5'-monophosphate (cAMP) in the postsynaptic cell and/or in the presynaptic terminal produced by blockade of phosphodiesterases leads to enhanced synaptic transmission in the CA1 area of the hippocampus and ii) that a low KM, Ca2+/calmodulin-independent cAMP-phosphodiesterase is an important component involved in the regulation of the intracellular cAMP level at synapses of central nervous system neurons.

1-Methyl-3-isobutylxanthine↗

PubMed1990

Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist.

1. Intracellular microelectrodes were used to obtain recordings from neurons in layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of the neocortex was used to evoke postsynaptic potentials. Graded series of stimulation were employed to selectively activate different classes of postsynaptic responses. The sensitivity of postsynaptic potentials and iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As reported previously, low-intensity electrical stimulation of cortical layer IV evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner. Stimulation at intensities just subthreshold for activation of inhibitory postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of stimulus intensities at or just below threshold for evoking an action potential, complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This effect was reversible on washing. This disinhibition could lead to enhanced excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate produced a membrane depolarization with superimposed action potentials, whereas NMDA depolarized the membrane potential and evoked bursts of action potentials. At concentrations up to 5 microM, CNQX selectively antagonized quisqualate responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX depression of NMDA responses.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1989

Transient and selective blockade of adenosine A1-receptors by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) causes sustained epileptiform activity in hippocampal CA3 neurons of guinea pigs.

The effects of endogenously released adenosine on the excitability of hippocampal neurons were studied using the novel and highly selective adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Extra- and intracellular recordings performed in area CA1 and CA3 of the guinea pig hippocampal slice preparation revealed that a transient suppression of an inhibitory purinergic tonus by DPCPX leads to sustained interictal-like epileptiform activity arising in area CA3. Once induced, the spontaneous burst discharges were apparently irreversible within the observation period, even after prolonged washout (2-3 h) in normal solution. In contrast, the hyperpolarizing action of exogenous adenosine, which was substantially reduced by DPCPX, recovered within 30-60 min of drug washout, indicating that DPCPX was not irreversibly bound to the A1-receptor.

Action Potentials↗

PubMed1989

Cholinergic modulation of epileptiform activity in the developing rat neocortex.

The effects of carbachol on picrotoxin-induced epileptiform activity and membrane properties of neurons in the developing rat neocortex were examined in an in vitro slice preparation. Intracellular recordings were obtained in layer II-III neurons of slices prepared from rats 9-21 days of age. Epileptiform activity in 9- to 14-day-olds consisted of a sharply rising, sustained (10-30 s) membrane depolarization with superimposed action potentials. Bath application of carbachol (5-50 microM) raised the threshold for evoking epileptiform activity but, when such responses were evoked, their underlying depolarizations were increased in amplitude. Orthodromic stimulation in slices from 15- to 21-day-old animals evoked a prolonged epileptiform burst response that triggered an episode of spreading depression (SD). Carbachol reduced epileptiform responses and suppressed the occurrence of SD. It did not significantly affect the resting membrane potential or the height of the action potential but decreased the rheobase current needed to evoke an action potential and increased the input resistance. All effects of carbachol were antagonized by atropine (1 microM). These results indicate that carbachol has both pre- and postsynaptic effects in the developing neocortex and can significantly modulate neuronal excitability in the immature nervous system.

Action Potentials↗