Dual Actions of Volatile Anesthetics on GABAAIPSCs 

1999 ◽  
Vol 90 (1) ◽  
pp. 120-134 ◽  
Author(s):  
Matthew I. Banks ◽  
Robert A. Pearce
Keyword(s):  
Concentration Dependence ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Volatile Anesthetics ◽  
Blocking Effect ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Baseline Noise ◽  
Volatile Agents

Background Volatile agents alter inhibitory postsynaptic currents (IPSCs) at clinically relevant concentrations, an action that is thought to make an important contribution to their behavioral effects. The authors investigated the mechanisms underlying these effects by evaluating the concentration dependence of modulation by enflurane, isoflurane, and halothane of IPSCs in rat hippocampal slices. Methods Action potential-independent gamma-aminobutyric acid(A) IPSCs (miniature IPSCs [mIPSCs]) were recorded from CA1 pyramidal neurons. The effects on mIPSC amplitude were used to distinguish between presynaptic (altered release) and postsynaptic (altered receptor response) actions of volatile agents. The concentration dependence of blocking and prolonging actions was compared among the volatile agents to determine whether a single modulatory process could account for both effects. Results The application of volatile anesthetics prolonged the decay and reduced the amplitude of mIPSCs in a dose-dependent manner. The effects on decay time for isoflurane and enflurane could not be distinguished. However, the blocking effect of enflurane was significantly greater than that of isoflurane at all concentrations. Despite the blocking effect, the net action of these agents was enhanced inhibition, because charge transfer was always significantly greater than control. Isoflurane, and to a lesser extent enflurane and halothane, caused a picrotoxin-sensitive increase in baseline noise. Moderate increases in mIPSC frequency were also observed for all agents. Conclusions These results show that enflurane, isoflurane, and halothane reduce IPSC amplitude through a direct postsynaptic action. Furthermore, the concentration dependence of the actions of the agents reveals a dissociation between the effects on the amplitude and the time course of IPSCs, suggesting that distinct mechanisms underlie the two actions.

Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering

1994 ◽  
Vol 71 (1) ◽  
pp. 1-10 ◽  
Author(s):  
S. A. Helekar ◽  
J. L. Noebels
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Channel Blockers ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Ca3 Pyramidal Neurons ◽  
The Difference

1. Intracellular current- and voltage-clamp recordings were carried out in CA3 pyramidal neurons from hippocampal slices of adult tg/tg mice and their coisogenic C57BL/6J (+/+) controls with the use of the single-electrode switch-clamp technique. The principal aim of this study was to investigate the mechanisms responsible for the tg gene-linked prolongation (mean 60%) of a giant synaptic response, the potassium-induced paroxysmal depolarizing shift (PDS) at depolarized membrane potentials (Vm -47 to -54 mV) during synchronous network bursting induced by 10 mM potassium ([K+]o). 2. To examine the role of intrinsic voltage-dependent conductances underlying the mutant PDS prolongation, neurons were voltage clamped by the use of microelectrodes filled with 100 mM QX-314 or QX-222 chloride (voltage-gated sodium channel blockers) and 2 M cesium sulphate (potassium channel blocker). The whole-cell currents active during the PDS showed a significantly prolonged duration (mean 34%) at depolarized Vms in tg/tg compared with +/+ cells, indicating that a defect in voltage-dependent conductances is unlikely to completely account for the mutant phenotype. 3. Bath application of 40 microM (DL)-2-aminophosphonovalerate (DL-APV) produced a 30% reduction in PDS duration in both genotypes but failed to significantly alter the tg gene-linked prolongation compared with the wild type. These data indicate that the mutant PDS abnormality does not result from a selective increase of the N-methyl-D-aspartate (NMDA) receptor-mediated excitatory synaptic component. 4. Blockade of gamma-aminobutyric acid-A (GABAA) transmission with picrotoxin (50 microM) or bicuculline (1–5 microM) completely eliminated the difference in PDS duration between the genotypes. Furthermore, although both GABAA receptor antagonists increased the mean PDS duration in +/+ neurons, they did not significantly alter it in tg/tg neurons. These findings are consistent with a reduction in GABAA receptor-mediated synaptic inhibition during bursting in the tg CA3 hippocampal network. 5. To test this hypothesis, bursting CA3 pyramidal neurons were loaded intracellularly with chloride by the use of KCl-filled microelectrodes to examine the effect of reversing the hyperpolarizing chloride-dependent GABAA receptor-mediated inhibitory postsynaptic component of the PDS. Chloride loading prolonged PDS duration in both genotypes, but the increase was greater in +/+ than in tg/tg neurons, indicating that a smaller GABAA inhibitory postsynaptic potential (IPSP) component was reversed in the mutant.(ABSTRACT TRUNCATED AT 400 WORDS)

Protein Kinase A Mediates the Modulation of the Slow Ca2+-Dependent K+ Current,I sAHP, by the Neuropeptides CRF, VIP, and CGRP in Hippocampal Pyramidal Neurons

2000 ◽  
Vol 83 (4) ◽  
pp. 2071-2079 ◽  
Author(s):  
Trude Haug ◽  
Johan F. Storm
Keyword(s):  
Protein Kinase ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Cell Voltage ◽  
Dependent Protein Kinase ◽  
Hippocampal Pyramidal Neurons ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Camp Cascade

We have studied modulation of the slow Ca2+-activated K+current ( I sAHP) in CA1 hippocampal pyramidal neurons by three peptide transmitters: corticotropin releasing factor (CRF, also called corticotropin releasing hormone, CRH), vasoactive intestinal peptide (VIP), and calcitonin gene–related peptide (CGRP). These peptides are known to be expressed in interneurons. Using whole cell voltage clamp in hippocampal slices from young rats, in the presence of tetrodotoxin (TTX, 0.5 μM) and tetraethylammonium (TEA, 5 mM), I sAHP was measured after a brief depolarizing voltage step eliciting inward Ca2+ current. Each of the peptides CRF (100–250 nM), VIP (400 nM), and CGRP (1 μM) significantly reduced the amplitude of I sAHP. Thus the I sAHP amplitude was reduced to 22% by 100 nM CRF, to 17% by 250 nM CRF, to 22% by 400 nM VIP, and to 40% by 1 μM CGRP. We found no consistent concomitant changes in the Ca2+ current or in the time course of I sAHP for any of the three peptides, suggesting that the suppression of I sAHP was not secondary to a general suppression of Ca2+ channel activity. Because each of these peptides is known to activate the cyclic AMP (cAMP) cascade in various cell types, and I sAHP is known to be suppressed by cAMP via the cAMP-dependent protein kinase (PKA), we tested whether the effects on I sAHP by CRF, VIP, and CGRP are mediated by PKA. Intracellular application of the PKA-inhibitor Rp-cAMPS significantly reduced the suppression of I sAHP by CRF, VIP, and CGRP. Thus with 1 mM Rp-cAMPS in the recording pipette, the average suppression of I sAHP was reduced from 78 to 26% for 100 nM CRF, from 83 to 32% for 250 nM CRF, from 78 to 30% for 400 nM VIP, and from 60 to 7% for 1 μM CGRP. We conclude that CRF, VIP, and CGRP suppress the slow Ca2+-activated K+ current, I sAHP, in CA1 hippocampal pyramidal neurons by activating the cAMP-dependent protein kinase, PKA. Together with the monoamine transmitters norepinephrine, serotonin, histamine, and dopamine, these peptide transmitters all converge on the cAMP cascade modulating I sAHP.

scholarly journals Ontogenesis of Presynaptic GABAB Receptor-Mediated Inhibition in the CA3 Region of the Rat Hippocampus

1998 ◽  
Vol 79 (3) ◽  
pp. 1341-1348 ◽  
Author(s):  
Olivier Caillard ◽  
Heather A. McLean ◽  
Yehezkel Ben-Ari ◽  
Jean-Luc Gaïarsa
Keyword(s):  
Pyramidal Neurons ◽  
Gabab Receptor ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Rat Hippocampus ◽  
Dependent Manner ◽  
Paired Pulse ◽  
Ca3 Pyramidal Neurons ◽  
Paired Pulse Depression ◽  
Ca3 Region

Caillard, Olivier, Heather A. McLean, Yehezkel Ben-Ari, and Jean-Luc Gaı̈arsa. Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. J. Neurophysiol. 79: 1341–1348, 1998. γ-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5–7 day old) and adult (27–34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and d(−)2-amino-5-phosphovaleric acid (d-AP5, 50 μM) with 2(triethylamino)- N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blockedb y  P - 3 - a m i n o p r o p y l - P - d i e t h o x y m e t h y l  p h o s p h o r i c  a c i d(CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 μM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.

The K+ channel opener diazoxide enhances glutamatergic currents and reduces GABAergic currents in hippocampal neurons

1993 ◽  
Vol 69 (2) ◽  
pp. 494-503 ◽  
Author(s):  
V. Crepel ◽  
C. Rovira ◽  
Y. Ben-Ari
Keyword(s):  
Intracellular Recording ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Reversal Potential ◽  
Input Resistance ◽  
Katp Channels ◽  
K Channel ◽  
Gamma Aminobutyric Acid ◽  
Postsynaptic Potentials

1. The effect of diazoxide, an opener of ATP-sensitive K+ channels (KATP channels) has been investigated in the rat hippocampal slices by the use of extracellular and intracellular recording techniques. 2. In control solution, diazoxide enhanced the CA1 and CA3 field excitatory postsynaptic potentials (EPSPs) and produced interictal activities in CA3. These effects were neither prevented by KATP blockers, including glibenclamide (3-30 microM) or tolbutamide (500 microM), nor mimicked by another KATP opener such as galanine (1 microM); thus these effects are probably not mediated by KATP channels. 3. Using intracellular recording, we then studied, in CA3 pyramidal neurons, the effect of diazoxide on the EPSPs and the fast and slow inhibitory postsynaptic potentials (IPSPs). 4. In presence of bicuculline (10 microM) and phaclofen (50 microM), to block, respectively, fast and slow IPSPs, diazoxide reversibly enhanced the EPSPs. 5. In presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM), to block EPSPs, diazoxide reversibly decreased both fast and slow IPSPs. 6. These effects of diazoxide on the EPSPs and fast and slow IPSPs were associated neither with a change of the reversal potential of the EPSPs or the fast and slow IPSPs nor with a change of the input resistance and membrane potential. 7. Using single electrode voltage-clamp technique, we then tested the effects of diazoxide on the currents generated by applications of glutamate or gamma-aminobutyric acid (GABA) -A and -B analogues. 8. In presence of tetrodotoxin (TTX; 1 microM), diazoxide reversibly enhanced the peak currents evoked by alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA; 3-5 microM), quisqualate (5-10 microM) and N-methyl-D-aspartate (NMDA; 10 microM), but not those evoked by kainate (1-3 microM). 9. In presence of TTX (1 microM), diazoxide reversibly decreased the GABA- (1-5 mM), isoguvacine- (30-60 microM), and baclofen- (10-30 microM) mediated peak currents. 10. It is concluded that, in the hippocampus, diazoxide enhances the excitatory glutamatergic currents and reduces the GABAergic inhibition, thus generating paroxystic activities. We suggest that these effects are mediated by second messenger cascades.

Dendritic origin of late events in optical recordings from salamander olfactory bulb

1992 ◽  
Vol 68 (3) ◽  
pp. 786-806 ◽  
Author(s):  
A. R. Cinelli ◽  
B. M. Salzberg
Keyword(s):  
Olfactory Bulb ◽  
Time Course ◽  
Slow Component ◽  
Field Potential ◽  
Olfactory Nerve ◽  
Nerve Fibers ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Direct Stimulation ◽  
Compound Action

1. Optical recordings of membrane-potential changes were used to characterize the origin and properties of the electrical signals from the dendritic level in slices of the salamander olfactory bulb. 2. The optical events were correlated with field-potential waves recorded simultaneously. Both responses exhibited patterns similar to those found in other species. 3. Orthodromic stimulation evoked a compound action potential in the olfactory nerve fibers, followed by two additional principal waves (N1 and N2). These field-potential waves reflected excitatory postsynaptic potentials at the primary mitral/tufted and granule cell dendrites, respectively. 4. Extrinsic optical signals from horizontal slices stained with the pyrazo-oxonal dye RH-155 showed a characteristic sequence of depolarizing and hyperpolarizing events. All of the signals exhibited a wavelength dependence expected for this dye and were abolished in the presence of high K+ in the bath. 5. According to their time courses, depolarizing responses under normal recording conditions were divided into two components, fast and slow. Orthodromic stimuli evoked a fast presynaptic response that represents synchronous compound action potentials from olfactory nerve fibers. At subglomerular levels, additional fast responses could often be recorded at the peri/subglomerular level and in the mitral/tufted somata region. These postsynaptic responses partially coincided with the rising phase of a different depolarizing signal, a slow component characterized by its prolonged time course. 6. With orthodromic stimulation, this slow signal attained its largest amplitude in the zone between the glomeruli and the superficial part of the external plexiform layer (EPL). Antidromic stimuli evoked a signal with some similarities to the one evoked orthodromically, but originating in deeper EPL regions. 7. Slow components were characterized by their Ca dependence. Low Ca2+ medium, or calcium channel blockers, suppressed this optical component, whether evoked orthodromically, antidromically, or by direct stimulation. In addition, Ba2+ (2.5–3.6 mM) in the bath did not abolish these responses, suggesting that they do not reflect a glial depolarization in response to elevated extracellular K+ concentration ([K+]o). 8. Locally applied stimuli next to the glomerular layer elicited these signals in 5–10 microM tetrodotoxin (TTX) or in low extracellular Na+ concentration ([Na+]o) medium, but antidromic or orthodromic stimuli failed to evoke the response under these conditions. The sizes of the responses to local stimuli remained constant, but an increase in their duration was observed in either TTX or low [Na+]o. 9. gamma-Aminobutyric acid (GABA) and baclofen reduced the size of the slow components in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)

Agent-selective Effects of Volatile Anesthetics on GABAAReceptor–mediated Synaptic Inhibition in Hippocampal Interneurons

2001 ◽  
Vol 94 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Koichi Nishikawa ◽  
M. Bruce MacIver
Keyword(s):  
Gabaa Receptor ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Volatile Anesthetics ◽  
Stratum Radiatum ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Ca1 Region ◽  
Whole Cell Patch Clamp ◽  
Cortical Regions

Background A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. Methods Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. Results Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. Conclusions Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

Quinolones and fenbufen interact with GABAA receptor in dissociated hippocampal cells of rat

1991 ◽  
Vol 66 (2) ◽  
pp. 497-504 ◽  
Author(s):  
N. Akaike ◽  
T. Shirasaki ◽  
T. Yakushiji
Keyword(s):  
Gabaa Receptor ◽  
Pyramidal Neurons ◽  
Equilibrium Potential ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Patch Clamp Technique ◽  
Concentration Dependent Manner ◽  
Inflammatory Agent ◽  
Quinolone Antibiotics ◽  
Anti Inflammatory

1. Interaction of quinolone antibiotics and the anti-inflammatory agent fenbufen with the gamma-aminobutyric acid-A (GABAA) receptor-chloride channel complex in pyramidal neurons freshly dissociated from the hippocampal CA1 region of the rats was investigated in whole-cell mode, using the patch-clamp technique under voltage-clamp conditions. 2. Quinolones in clinical doses had no effects on the GABA-gated Cl- current (ICl) but slightly suppressed the response at concentrations greater than 10(-5) M. A metabolite of fenbufen, 4-biphenylacetic acid (BPA), also had little effect on the GABA response at therapeutic concentrations. 3. Coadministration of one of quinolones and BPA suppressed the GABA-gated ICl with increase in each of them in a concentration-dependent manner, and there was a parallel shift of the concentration-response curve for GABA to the right but with no effect on the maximum response, thereby indicating a competitive antagonism. The inhibitory potency of antibiotics in combination with BPA was in the order of norfloxacin much greater than enoxacin greater than cyprofloxacin greater than pipemidic acid much greater than ofloxacin greater than cinoxacin = piromidic acid = nalidixic acid = 0. 4. Norfloxacin and BPA, administered simultaneously, also strongly suppressed pentobarbital sodium (PB)-gated ICl, but they did not act on benzodiazepine (BZP) receptors. 5. Both GABA- and PB-induced ICls reversed at the Cl- equilibrium potential (ECl). In the presence of BPA, the quinolone-induced inhibition of GABA-gated ICls showed no voltage dependence. 6. It was concluded that, in the presence of an anti-inflammatory agent, the quinolone antibiotics decrease the affinity of GABAA receptors, the result being induction of epileptogenic neurotoxicities.

scholarly journals DM1 Transgenic Mice Exhibit Abnormal Neurotransmitter Homeostasis and Synaptic Plasticity in Association with RNA Foci and Mis-Splicing in the Hippocampus

2022 ◽  
Vol 23 (2) ◽  
pp. 592
Author(s):  
Brigitte Potier ◽  
Louison Lallemant ◽  
Sandrine Parrot ◽  
Aline Huguet-Lachon ◽  
Geneviève Gourdon ◽  
...  
Keyword(s):  
Time Course ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Glutamate Uptake ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Synaptic Dysfunction ◽  
Functional Changes ◽  
Rna Foci ◽  
The Impact

Myotonic dystrophy type 1 (DM1) is a severe neuromuscular disease mediated by a toxic gain of function of mutant RNAs. The neuropsychological manifestations affect multiple domains of cognition and behavior, but their etiology remains elusive. Transgenic DMSXL mice carry the DM1 mutation, show behavioral abnormalities, and express low levels of GLT1, a critical regulator of glutamate concentration in the synaptic cleft. However, the impact of glutamate homeostasis on neurotransmission in DM1 remains unknown. We confirmed reduced glutamate uptake in the DMSXL hippocampus. Patch clamp recordings in hippocampal slices revealed increased amplitude of tonic glutamate currents in DMSXL CA1 pyramidal neurons and DG granule cells, likely mediated by higher levels of ambient glutamate. Unexpectedly, extracellular GABA levels and tonic current were also elevated in DMSXL mice. Finally, we found evidence of synaptic dysfunction in DMSXL mice, suggestive of abnormal short-term plasticity, illustrated by an altered LTP time course in DG and in CA1. Synaptic dysfunction was accompanied by RNA foci accumulation in localized areas of the hippocampus and by the mis-splicing of candidate genes with relevant functions in neurotransmission. Molecular and functional changes triggered by toxic RNA may induce synaptic abnormalities in restricted brain areas that favor neuronal dysfunction.

scholarly journals Anti-Müllerian Hormone Regulation of Synaptic Transmission in the Hippocampus Requires MAPK Signaling and Kv4.2 Potassium Channel Activity

2021 ◽  
Vol 15 ◽  
Author(s):  
Kang Wang ◽  
Fuhua Xu ◽  
James Maylie ◽  
Jing Xu
Keyword(s):  
Synaptic Transmission ◽  
P38 Mapk ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Hormone Regulation ◽  
Paracrine Factor ◽  
Specific Expression ◽  
Hippocampal Pyramidal Neurons

Anti-Müllerian hormone (AMH) is a paracrine factor generated peripherally by the gonads to regulate gonadal function in adult mammals. We recently reported that AMH and AMH-specific receptor Anti-Müllerian hormone receptor 2 (AMHR2) are expressed in the hippocampus, and exogenous AMH protein rapidly increased synaptic transmission and long-term synaptic plasticity at the CA3-CA1 synapses. Here we examined the cell-specific expression of AMHR2 and the cellular mechanism of rapid boosting effect of AMH on synaptic transmission in mouse hippocampus. Immunofluorescence staining showed that AMHR2 was specifically expressed in the soma and dendrites of hippocampal pyramidal neurons, but not glial cells. Electrophysiological recordings on acute hippocampal slices showed that AMH did not affect AMPAR-mediated or N-Methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic currents at the CA3-CA1 synapses. The small-conductance Ca2+-activated K+ channel (SK2) and A-type K+ channel (Kv4.2) contribute to shaping excitatory postsynaptic potentials (EPSPs) at the CA3-CA1 synapses. Bath application of apamin to block SK2 did not alter AMH effect on increasing EPSPs, whereas blocking Kv4.2 channel with 4-aminopyridine, or chelating internal Ca2+ with BAPTA occluded the action of AMH on boosting EPSPs. Kv4.2 activity is regulated by p38 mitogen-activated kinase (MAPK). Blocking p38 MAPK with SB203580 occluded the effect of AMH on increasing EPSPs. These results show that Kv4.2 channel contributes to the rapid action of AMH on boosting synaptic transmission in a Ca2+- and p38 MAPK-dependent manner. Our findings provide functional evidence that AMH enhances synaptic transmission through Kv4.2 channel in the hippocampus, suggesting a possible role of Kv4.2 channel in AMH-regulated neuronal process underlying learning and memory.

Volatile Anesthetics Increase Intracellular Calcium in Cerebrocortical and Hippocampal Neurons 

1999 ◽  
Vol 90 (4) ◽  
pp. 1137-1145 ◽  
Author(s):  
Christoph H. Kindler ◽  
Helge Eilers ◽  
Paul Donohoe ◽  
Surhan Ozer ◽  
Philip E. Bickler
Keyword(s):  
Intracellular Calcium ◽  
Hippocampal Neurons ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Free Medium ◽  
Ca1 Neurons

Background An increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+]i conflict. Methods Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+-release inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM) and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane (445 microM) also were performed. Results Isoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05). Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05). Conclusions (1) Isoflurane and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]i is caused primarily by release from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.

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