Strychnine-induced potassium current in CA1 pyramidal neurones of the rat hippocampus.

1. Direct actions of strychnine (Str) and brucine (Bru) on the dissociated hippocampal CA1 neurones of the rat have been investigated with the whole-cell mode of the patch-clamp technique. 2. At a holding potential (VH) of -20 mV, both Str and Bru elicited outward current at concentrations over 10(-5) M. The reversal potential of Str-induced current (EStr) was -77.8 mV, which was close to the K+ equilibrium potential (EK = -80.3 mV). The change in EStr for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. 3. The concentration-response curves for Str and Bru were bell-shaped, and nearly maximum response occurred at 10(-4) M for Str and 3 x 10(-4) M for Bru. The maximum current amplitude induced by Bru was about 80% of that induced by Str. A transient 'hump' current appeared immediately after the wash-out of external solutions containing Str and Bru at concentrations higher than 10(-4) and 3 x 10(-4) M, respectively. 4. The Str-induced current (IStr) was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. IStr was insensitive to glibenclamide, a blocker of ATP-sensitive K+ channels. 5. Internal perfusion with 10 mM BAPTA did not affect the Str-induced IK. Depletion of the intracellular Ca2+ store by caffeine had no effect, indicating that intracellular Ca2+ does not mediate the Str-induced activation of K+ conductance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tandospirone-induced K+ current in acutely dissociated rat dorsal raphe neurones

1. The effects of tandospirone (TDS) on dissociated rat dorsal raphe neurones were investigated using the patch-clamp method.
2. Under current-clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of firing rates.
3. Under voltage-clamp conditions, TDS induced an inward rectifying K⁺ current in a concentration-dependent manner.
4. The TDS-induced K⁺ currents (I_TDS) were mimicked by 8-OH-DPAT, a 5-HT_1A agonist. The I_TDS was blocked by spiperone, a 5-HT_1A receptor antagonist, in a concentration-dependent manner.
5. N-Ethylmaleimide, an agent which uncouples between the receptor and the G-protein, irreversibly blocked the I_TDS.
6. In neurones perfused intracellularly with a pipette-solution containing GTP using the conventional whole-cell patch recording, the I_TDS showed a gradual rundown. When the neurones were perfused with GTPγS, TDS activated the inwardly rectifying K⁺ current in an irreversible manner.
7. In the inside-out patch recording mode, TDS-activated single K⁺ channel currents (i_TDS) which also showed an inward rectification. When the GDP in cytosolic side was completely replaced with GTP, the open probability of i_TDS significantly increased.
8. These results indicate that the activation of 5-HT_1A receptors by TDS directly opens the inward rectifying K⁺ channels via a G-protein mediated process.

     

Effects of sodium metabisulfite on potassium currents in acutely isolated CA1 pyramidal neurons of rat hippocampus.

The effects of sodium metabisulfite (SMB), a food preservative mostly used in food and drug industries, on voltage-dependent potassium currents in acutely isolated hippocampal CA1 pyramidal neurons of rat were studied using the whole-cell patch-clamp techniques. SMB increased transient outward potassium current (IA) and delayed rectifier potassium current (IK) in a concentration-dependent manner. 10 microM SMB shifted the steady-state activation curve of IK to more negative potentials, and the steady-state inactivation curves of IA and IK to more positive potentials. Time to peak of IA was not affected, but the decay of IA was delayed by SMB. However, the activation and inactivation time constants of IK were both decreased by SMB. These results suggested that SMB differently affected IA and IK, and it would decrease the excitability of hippocampal neuron by increasing potassium currents.     

Activation of BKCa channels in acutely dissociated neurones from the rat ventromedial hypothalamus by NS 1619.

NS 1619 activates the large-conductance Ca(2+)-dependent K+ channel (BKCa) in membrane patches isolated from rat ventromedial hypothalamic neurones. The activation is concentration dependent, with a maximal effect at less than 30 microM, reversible and can be inhibited by application of iberiotoxin to the extracellular membrane. NS 1619 does not activate ATP-K+ channels present in the same neurones.     

Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurones

1. The effect of ophiopogonin-D (OP-D), a steroidal glycoside and an active component of Bakumondo-to, a Chinese herbal antitussive, on neurones acutely dissociated from paratracheal ganglia of 2-week-old Wistar rats was investigated using the nystatin-perforated patch recording configuration. 2. Under current-clamp conditions, OP-D (10 microM) hyperpolarized the paratracheal neurones from a resting membrane potential of -65.7 to -73.5 mV. 3. At the concentration of 1 microM and above, OP-D concentration-dependently activated an outward current accompanied by an increase in the membrane conductance under voltage-clamp conditions at a holding potential of -40 mV. 4. The reversal potential of the OP-D-induced current (I(OP-D)) was -79.4 mV, which is close to the K(+) equilibrium potential of -86.4 mV. The changes in the reversal potential for a 10 fold change in extracellular K(+) concentration was 53.1 mV, indicating that the current was carried by K(+). 5. The I(OP-D) was blocked by an extracellular application of 1 mM Ba2+ by 59.0%, but other K(+) channel blockers, including 4-aminopyridine (3 mM), apamin (1 microM), charybdotoxin (0.3 microM), glibenclamide (1 microM), tolbutamide (0.3 mM) and tetraethylammonium (10 mM), did not inhibit the I(OP-D). 6. OP-D also inhibited the ACh- and bradykinin-induced depolarizing responses which were accompanied with firing of action potentials. 7. The results suggest that OP-D may be of benefit in reducing the excitability of airway parasympathetic ganglion neurones and consequently cholinergic control of airway function and further, that the hyperpolarizing effect of OP-D on paratracheal neurones via an activation of K(+) channels might explain a part of mechanisms of the antitussive action of the agent.     

山奈酚对急性短暂缺氧时大鼠海马CA1神经元电压依赖性钾通道的作用

目的研究山奈酚对正常和急性短暂缺氧时大鼠海马CA1锥体神经元电压依赖性钾通道的作用.方法急性分离大鼠海马CA1区锥体神经元,采用全细胞记录,用含有氰化钾(KCN)60μmol·L-1的标准外液灌流模拟细胞缺氧,观察山奈酚对正常和缺氧时海马CA1区神经元电压依赖性钾通道的作用.结果山奈酚对正常和缺氧时海马CA1神经元电压依赖性K 电流有明显的抑制作用,可同时抑制瞬时外向型钾电流(IA)和延迟整流性钾电流(Ik),具有浓度依赖和电压依赖性;山奈酚对IA的半数抑制浓度(IC50)约为50μmol·L-1,对IK的IC50约为80μmol·L-1.结论山奈酚对正常和缺氧时大鼠海马CA1神经元电压依赖性钾通道有抑制作用,其对钾通道的抑制作用可能参与脑缺血保护.     

Pharmacology of postsynaptic metabotropic glutamate receptors in rat hippocampal CA1 pyramidal neurones.

1. Activation of metabotropic glutamate receptors (mGluRs) in hippocampal CA1 pyramidal neurones leads to a depolarization, an increase in input resistance and a reduction in spike frequency adaptation (or accommodation). At least eight subtypes of mGluR have been identified which have been divided into three groups based on their biochemical, structural and pharmacological properties. It is unclear to which group the mGluRs which mediate these excitatory effects in hippocampal CA1 pyramidal neurones belong. We have attempted to address this question by using intracellular recording to test the effects of a range of mGluR agonists and antagonists, that exhibit different profiles of subtype specificity, on the excitability of CA1 pyramidal neurones in rat hippocampal slices. 2. (2S, 1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1) caused a reduction in spike frequency adaptation and a depolarization (1-10 mV) associated with an increase in input resistance (10-30%) at concentrations (> or = 50 microM) that have been shown to activate mGluRs in groups I, II and III. Similar effects were observed with concentrations (50-100 microM) of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) and (1S,3S)-ACPD that exhibit little or no activity at group III mGluRs but which activate groups I and II mGluRs. 3. Inhibition of the release of endogenous neurotransmitters through activation of GABAB receptors, by use of 200 microM (+/-)-baclofen, did not alter the effects of (1S,3R)-ACPD (50-100 microM), (1S,3S)-ACPD (100 microM) or L-CCG1 (100 microM). This suggests that mGluR agonists directly activate CA1 pyramidal neurones. 4. Like these broad spectrum mGluR agonists, the racemic mixture ((SR)-) or resolved (S)-isomer of the selective group I mGluR agonist 3,5-dihydroxyphenylglycine ((SR)-DHPG (50-100 microM) or (S)-DHPG (20-50 microM)) caused a reduction in spike frequency adaptation concomitant with postsynaptic depolarization and an increase in input resistance. In contrast, 2S,1'R,2'R,3'R-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV; 100 microM) and (S)-2-amino-4-phosphonobutanoic acid (L-AP4; 100-500 microM), which selectively activate group II mGluRs and group III mGluRs, respectively, had no effect on the passive membrane properties or spike frequency adaptation of CA1 pyramidal neurones. 5. The mGluR antagonists (+)-alpha-methyl-4-carboxyphenylglycine ((+)-MCPG; 1000 microM) and (S)-4-carboxyphenylglycine ((S)-4CPG; 1000 microM), which block groups I and II mGluRs and group I mGluRs, respectively, had no effect on membrane potential, input resistance or spike frequency adaptation per se.(ABSTRACT TRUNCATED AT 400 WORDS)     

Trichloroethanol potentiation of gamma-aminobutyric acid-activated chloride current in mouse hippocampal neurones.

1. The action of 2,2,2-trichloroethanol on gamma-aminobutyric acid (GABA)-activated Cl- current was studied in mouse hippocampal neurones in tissue culture by use of whole-cell patch-clamp recording. 2. Trichloroethanol increased the amplitude of currents activated by 1 microM GABA or 0.1 microM muscimol. Trichloroethanol, 1-25 mM, potentiated current activated by 1 microM GABA in a concentration-dependent manner with an EC50 of 3.0 +/- 1.4 mM and a maximal response (Emax) of 576 +/- 72% of control. 3. Trichloroethanol potentiated currents activated by GABA concentrations < 10 microM, but did not increase the amplitude of currents activated by concentrations of GABA > or = 10 microM. Despite marked potentiation of currents activated by low concentrations of GABA, trichloroethanol did not significantly alter the EC50, slope, or Emax of the GABA concentration-response curve. 4. Trichloroethanol, 5 mM, potentiated GABA-activated current in neurones in which ethanol, 10-500 mM, did not. The effect of trichloroethanol was not altered by the putative ethanol antagonist, Ro 15-4513. Trichloroethanol did not potentiate currents activated by pentobarbitone. 5. In the absence of exogenous GABA, trichloroethanol at concentrations > or = 2.5 mM activated a current that appeared to be carried by Cl- as its reversal potential changed with changes in the Cl- gradient and as it was inhibited by the GABAA antagonists, bicuculline methiodide and picrotoxin. 6. Since trichloroethanol is thought to be the active metabolite of chloral hydrate and other chloral derivative anaesthetics, potentiation of the GABA-activated current in central nervous system neurones by trichloroethanol may contribute to the sedative/hypnotic effects of these agents.     

Acetylcholine modulation of high-voltage-activated calcium channels in the neurones acutely dissociated from rat paratracheal ganglia

1. The modulation of high-voltage-activated (HVA) Ca²⁺ channels by acetylcholine (ACh) was studied in the paratracheal ganglion cells acutely dissociated from 2-week-old Wistar rats by use of the nystatin perforated patch recording configuration under voltage-clamp conditions.
2. ACh inhibited the HVA Ca²⁺ currents in a concentration- and voltage-dependent manner.
3. The inhibition was mimicked by a muscarinic agonist, oxotremorine. Pirenzepine and methoctramine produced parallel shifts to the right in the ACh concentration-response curves. Schild analysis of the ACh concentration-ratios yield pA₂ values for pirenzepine and methoctramine of 6.85 and 8.57, respectively, suggesting the involvement of an M₂ receptor.
4. Nifedipine, ω-conotoxin-GVIA and ω-conotoxin-MVIIC reduced the HVA I_Ca by 16.8, 59.2 and 6.3%, respectively. A current insensitive to all of these Ca²⁺ antagonists, namely `R-type'', was also observed. The results indicated the existence of L-, N-, P/Q-, and R-type Ca²⁺ channels.
5. The ACh-sensitive current component was markedly reduced in the presence of ω-conotoxin-GVIA, but not with both nifedipine and ω-conotoxin-MVIIC. ACh also inhibited the R-type HVA I_Ca remaining in saturating concentrations of nifedipine, ω-conotoxin-GVIA and ω-conotoxin-MVIIC.
6. The inhibitory effect of ACh was prevented by pretreatment with pertussis toxin.
7. It was concluded that ACh selectively reduces both the N- and R-type Ca²⁺ channels, by activating pertussis toxin sensitive G-protein through the M₂ muscarinic receptor in paratracheal ganglion cells.

     

Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones

1. The inhibitory effects of cilnidipine (FRC-8653) and various organic Ca²⁺ channel blockers on high voltage-activated Ba²⁺ currents (HVA I_Ba) in rat sympathetic neurones were examined by means of the conventional whole-cell patch-clamp recording mode under voltage-clamped conditions.
2. HVA I_Ba was classified into three different current components with subtype selective peptide Ca²⁺ channel blockers. No ω-Agatoxin IVA-sensitive (P-type) or ω-conotoxin MVIIC-sensitive (Q-type) current components were observed. Most (>85%) I_Ba was found to consist of ω-conotoxin GVIA-sensitive N-type components.
3. The application of cilnidipine inhibited HVA I_Ba in a concentration-dependent manner. The K_d value for cilnidipine was 0.8 μM. Cilnidipine did not shift the current-voltage (I-V) relationship for HVA I_Ba, as regards the threshold potential and peak potential where the amplitude reached a maximum.
4. High concentrations of three hypotensive Ca²⁺ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA I_Ba in a concentration-dependent manner. The K_d values for nifedipine, diltiazem and verapamil were 131, 151 and 47 μM, respectively. A piperazine-type Ca²⁺ channel blocker, flunarizine, showed a relatively potent blocking action on I_Ba. The K_d value was about 3 μM.
5. These results thus show that cilnidipine potently inhibits the sympathetic Ca²⁺ channels which predominantly consist of an ω-Cg-GVIA-sensitive component. This blockade of the N-type Ca²⁺ channel, as well as the L-type Ca²⁺ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.

     

Inhibition of slow Ca(2+)-activated K(+) current by 4-aminopyridine in rat hippocampal CA1 pyramidal neurones

1. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing current pulses were used to evoke a sAHP. The sAHP was blocked by low concentrations of carbacholine (Cch) but insensitive to high concentrations of apamin. 2. In the presence of extracellular 4-AP, the first dendritic sAHP evoked was reduced compared to a maximal sAHP evoked in the absence of 4-AP. The reduction was evident at submillimolar concentration and increased to about 80% with 4 mM 4-AP. 3. The stability of the 4-AP-induced block was affected by the type of anion used in the electrode solution. With K(+) acetate (KAc) or K(+) methylsulphate (KMeSO(4)) containing electrodes, the block was progressively removed during the initial 300 - 400 s of recordings. With KCl containing electrodes, the block remained stable and was 10% larger than that obtained with acetate. Detailed investigations showed that intracellular acetate promotes the removal of the 4-AP-induced block in an activity-dependent manner. 4. Intracellularly applied 4-AP also induced an acetate-sensitive block of the dendritic sAHP. 5. 4-AP also blocked the somatic sAHP and the stability of the block showed the same sensitivity towards anions as the dendritic sAHP. 6. Thus 4-AP appears to block the slow Ca(2+)-activated K(+) current underlying the sAHP in a complex manner which is sensitive to certain types of anions.     

Effects of philanthotoxin-343 on CA1 pyramidal neurons of rat hippocampus in vitro.

A synthetic analog of philanthotoxin-433, philanthotoxin-343 (PhTX-343), was tested in hippocampal pyramidal neurons in vitro. PhTX-343 (2 microM) did not significantly change synaptic transmission mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors in the CA1 region of hippocampus. However, PhTX-343 significantly suppressed both the synaptic N-methyl-D-aspartate receptor-induced current (NMDA) obtained in the presence of CNQX(6-cyano-7-nitroquinoxaline-2,3-dione)/picrotoxin (10 microM) and the directly evoked NMDA receptor-induced current to pressure ejection of NMDA in the presence of tetrodotoxin (0.5 microM). A short transient facilitation of both types of NMDA response was seen immediately after the beginning of PhTX-343 application. Our results suggest that at high concentration (2 microM) PhTX-343 inhibits the NMDA-gated current, while the early facilitation occurred during an initial low concentration of the compound. Both facilitative and depressive actions of PhTX-343 are localized at the postsynaptic membrane.     

Inhibition of delayed rectifier K+ currents by copper in acutely dissociated rat hippocampal CA1 neurons

A growing number of research results demonstrate that copper is an important trace element to life. In this study, whole-cell recording made from acutely dissociated rat hippocampal CA1 neurons was employed to investigate the actions of copper (Cu(2+)) on the delayed rectifier K(+) currents (I(K)). External application of various concentrations of Cu(2+) (1-1000microM) reduced the amplitude of I(K) in a dose-dependent manner with an IC(50) value of 100microM and a Hill coefficient of 0.4. 300microM of Cu(2+) depolarized the I(K) activation curves by 12.5mV and hyperpolarized the I(K) state-inactivation curves by 17.4mV, respectively. At this concentration, Cu(2+) also significantly increased the value of the fast decay time constant (tau(1)), but had no effect on the I(K) recovery from inactivation. These results suggest that relevant concentrations of copper at physiological and pathological level can influence the neuronal excitability of rat hippocampal CA1 neurons by voltage-gated delayed rectifier K(+) channels, and such actions are likely involved in the pathophysiology of Cu-related Wilson's disease.     

NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons.

N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 microM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons.     

Developmental regulation of AMPA-receptor properties in CA1 pyramidal neurons of rat hippocampus

AMPA-receptor (AMPA-R) currents were recorded from CA1 pyramidal neurons in situ and after acute isolation from the hippocampus of 3- to 45-day-old rats. Membrane currents were analyzed by combining the patch clamp method with fast application techniques. The complete block of receptor currents by GYKI 53655 and the absence of modulation by Concanavalin A indicated that the cells exclusively expressed non-NMDA glutamate receptors of the AMPA subtype while functional kainate receptors could not be detected. The lowest sensitivity to kainate and NBQX was observed at postnatal day (p) 18. These changes might reflect a lower abundance of GluR1 at that developmental stage. A decrease of potentiation of receptor currents by cyclothiazide (CTZ), an acceleration of the recovery from CTZ potentiation and a faster and more complete desensitization of glutamate-evoked currents suggest an up-regulation of flop splice variants with increasing age. These functional data indicate that AMPA-R expression in CA1 pyramidal neurons varies during postnatal development which can be expected to influence the kinetics of synaptic transmission and the excitotoxic vulnerability as well.     

Nicergoline inhibits T-type Ca2+ channels in rat isolated hippocampal CA1 pyramidal neurones.

1. The effects of nicergoline on the T- and L-type Ca2+ currents in pyramidal cells freshly isolated from rat hippocampal CA1 region were investigated by use of a 'concentration-clamp' technique. The technique combines a suction-pipette technique, which allows intracellular perfusion under a single-electrode voltage-clamp, and rapid exchange of extracellular solution within 2 ms. 2. T-type Ca2+ currents were evoked by step depolarizations from a holding potential of -100 mV to potentials more positive than -70 to -60 mV, and reached a peak at about -30 mV in the current-voltage relationship. Activation and inactivation of T-type Ca2+ currents were highly potential-dependent. 3. Nicergoline and other Ca2+ antagonists dose-dependently blocked the T-type Ca2+ channel with an order of potency nicardipine greater than nicergoline greater than diltiazem. 4. The L-type Ca2+ channel was also blocked in the order nicardipine greater than nicergoline greater than diltiazem, although the T-type Ca2+ channel was more sensitive to nicergoline. 5. The inhibitory effects of nicergoline and nicardipine on the T-type Ca2+ current were voltage-, time-, and use-dependent, and the inhibition increased with a decrease in the external Ca2+ concentration. Diltiazem showed only a use-dependent block.     

Effects of aluminum chloride on sodium current, transient outward potassium current and delayed rectifier potassium current in acutely isolated rat hippocampal CA1 neurons.

The effects of aluminum chloride (AlCl3) on sodium current (INa), the transient outward potassium (IA) and delayed rectifier potassium currents (IK) in hippocampal CA1 neurons of rats were studied using the whole cell patch-clamp technique. AlCl3 decreased INa, IA, and IK in a partly reversible, dose and voltage-dependent manner. AlCl3 prolonged the time to peak of INa, and increased the inactivation time constants of INa and IA . In addition, 1000 microM AlCl3 shifted the voltage dependence of steady-state activation of INa, IA and IK toward positive potential, and the voltage dependence of steady-state inactivation of INa, IA toward negative potential. These results imply that AlCl3 could affect the activation and inactivation courses of sodium current and potassium current of rat hippocampal CA1 neurons, which may contribute to damage of the central nervous system by aluminum.     

Cocaine decreases the glycine-induced Cl- current of acutely dissociated rat hippocampal neurons

The effects of cocaine on glycine-induced Cl- current (I(GLY)) of single neurons, freshly isolated from the rat hippocampal CA1 area, were studied with conventional whole-cell recording under voltage-clamp conditions. Cocaine depressed I(GLY) in a concentration-dependent manner, with an IC50 of 0.78 mM. Preincubation with 1 mM cocaine alone had no effect on I(GLY), suggesting that resting glycine channels are insensitive to cocaine. The depression of I(GLY) by cocaine was independent of membrane voltage. Internal cell dialysis with 1 mM cocaine failed to modify I(GLY). Because the depression of I(GLY) was noncompetitive, cocaine may act on the glycine receptor-chloride ionophore complex at a site distinct from that to which glycine binds. The cocaine suppression of I(GLY) was unaffected by 1 microM tetrodotoxin and 1 microM strychnine. Blockers of protein kinase C (Chelerythrine), kinase A (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl, (H-89)) and Ca-calmodulin-dependent kinase (1-[N,O-bis(5-isoquinoline-sulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaz ine (KN-62)) were also ineffective, which suggests that these phosphorylating mechanisms do not modulate cocaine-induced suppressant action on I(GLY). This extracellular, strychnine-independent depression of I(GLY) may contribute to cocaine-induced seizures.     

Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus.

Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or rise time of the currents but current amplitude was depressed at 200 microM. The prolongation of currents increased with drug concentration within the range tested (50 to 200 microM). Halothane, at concentrations from 1 to 5%, also increased the time constant of decay of i.p.s.cs. The effect increased with concentration and was fully reversible. Ketamine, at a concentration of 0.5 mM, increased the time constant of decay of i.p.s.cs by 50 to 80% and the effect was reversible. Ethanol (10-200 mM), nitrous oxide (75-80%), and caffeine (10 microM-5 mM) had no detectable effect on the i.p.s.cs. It is suggested that pentobarbitone, halothane and ketamine increase the time constant of decay of the i.p.s.cs by stabilizing the open state of channels activated by gamma-aminobutyric acid.     

Galanin blocks the slow cholinergic EPSP in CA1 pyramidal neurons from ventral hippocampus

Using intracellular recordings from slice preparations, we studied the effects of the peptide galanin on the properties of CA1 pyramidal neurons from rat ventral hippocampus. Galanin, applied in the superfusing medium, had a weak and inconsistent effect on the membrane potential or on the afterhyperpolarization which follows a train of spikes. Galanin, which is localized in some cholinergic neurons of the septo-hippocampal pathway, did not affect the action of acetylcholine or carbachol on CA1 pyramidal neurons. However, it did have a presynaptic inhibitory effect on the cholinergic terminals, blocking the slow cholinergic excitatory post-synaptic potential (EPSP) induced by the release of endogenous acetylcholine on the pyramidal neurons. This effect was reversible and mimicked by atropine. These results suggest that the peptide galanin, colocalized with acetylcholine in some septo-hippocampal neurons might play a role in the control of acetylcholine release.