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K Kaila

Publications and source records attributed to K Kaila.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synaptic activation of GABAA receptors induces neuronal uptake of Ca2+ in adult rat hippocampal slices.

Synaptically evoked transmembrane movements of Ca2+ in the adult CNS have almost exclusively been attributed to activation of glutamate receptor channels and the consequent triggering of voltage-gated calcium channels (VGCCs). Using microelectrodes for measuring free extracellular Ca2+ ([Ca2+]o) and extracellular space (ECS) volume, we show here for the first time that synaptic stimulation of gamma-aminobutyric acid-A (GABAA) receptors can result in a decrease in [Ca2+]o in adult rat hippocampal slices. High-frequency stimulation (100-200 Hz, 0.4-0.5 s) applied in stratum radiatum close (</=0.5 mm) to the recording site induced a 0.1- to 0.3-mM transient fall in [Ca2+]o from a baseline level of 1.6 mM. Concomitantly, a 30-40% decrease in the ECS volume was seen. Exposure of drug-naïve slices to the GABAA receptor antagonist picrotoxin (100 microM) first attenuated and only thereafter augmented the Ca2+ shifts. Application of ionotropic glutamate receptor antagonists resulted in a monotonic reduction of the Ca2+ response, but a large Ca2+ shift persisted (60-70% of the original), which was attenuated by a subsequent application of picrotoxin or bicuculline. In the absence of ionotropic glutamatergic transmission, pentobarbital sodium (100 microM), an up-modulator of the GABAA receptor, strongly enhanced the activity-evoked changes in [Ca2+]o. We suggest that the underlying mechanism of GABA-induced Ca2+ transients is the activation of VGCCs by bicarbonate-dependent GABA-mediated depolarizing postsynaptic potentials. Accordingly, stimulation-evoked Ca2+ shifts were inhibited by the membrane-permeant inhibitor of carbonic anhydrase, ethoxyzolamide (50 microM) or in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered HCO3-free solution. Neuronal Ca2+ uptake caused by intense synaptic activation of GABAA receptors may prove to be an important mechanism in the modulation of activity-dependent neuronal plasticity, epileptogenesis, and cell survival in the adult brain.

Animals↗
PubMed1998

Changes in [Ca2+]0 during anoxia in CNS white matter.

Irreversible anoxic injury of axons in the rat optic nerve requires the presence of extracellular Ca2+. To test the hypothesis that Ca2+ enters an intracellular compartment during anoxia we monitored [Ca2+]0 in this CNS white matter tract using ion-sensitive microelectrodes. Periods of anoxia lasting 15 min resulted in a rapid, reversible increase in [Ca2+]0 accompanied by transient loss of nerve conduction. This increase in [Ca2+]0 was apparently the result of extracellular space shrinkage. Anoxic periods lasting 60 min resulted in an initial rise followed by a sustained fall in [Ca2+]0, indicative of net influx of Ca2+ into an intracellular compartment. Following reoxygenation after 60 min of anoxia, [Ca2+]0 slowly returned toward control levels but nerve conduction recovered incompletely, indicating irreversible loss of function. Removal of bath Ca2+ lowered [Ca2+]0 to about 100 microM, prevented the anoxia-induced fall in [Ca2+]0, and protected against irreversible loss of the compound action potential.

Animals↗
PubMed1998

Sphingosine inhibits voltage-operated calcium channels in GH4C1 cells.

In the present study we investigated the mechanism of inhibitory action of sphingosine (SP) on voltage-activated calcium channels (VOCCs) in pituitary GH4C1 cells. Using the patch-clamp technique in the whole-cell mode, we show that SP inhibits Ba2+ currents (IBa) when 0.1 mM BAPTA is included in the patch pipette. However, when the BAPTA concentration was raised to 1-10 mM, SP was without a significant effect. The effect of SP was apparently not mediated via a kinase, as it was not inhibited by staurosporine. By using the double-pulse protocol (to release possible functional inhibition of the VOCCs by G proteins), we observed that G proteins apparently evoked very little functional inhibition of the VOCCs. Furthermore, including GDPbetaS (guanyl-5'-yl thiophosphate) in the patch pipette did not alter the inhibitory effect of SP on the Ba2+ current, suggesting that SP did not modulate the VOCCs via a G protein-dependent pathway. Single-channel experiments with SP in the pipette, and experiments with excised outside-out patches, suggested that SP directly inhibited VOCCs. The main mechanism of action was a dose-dependent prolongation of the closed time of the channels. The results thus show that SP is a potent inhibitor of VOCCs in GH4C1 cells, and that calcium may be a cofactor in this inhibition.

Animals↗
PubMed1998

Distribution of GABA receptor rho subunit transcripts in the rat brain.

The gamma-aminobutyric acid (GABA) receptor rho subunits recently cloned from rat and human retina are thought to form GABA receptor channels belonging to a pharmacologically distinct receptor class, termed GABA(C). In this work we have examined the distribution of rho1, rho2 and rho3 subunits, and found expression of all three transcripts in several regions of the rat nervous system. In situ hybridization revealed expression of rho2 in the adult rat retina and some other parts of the visual pathways. A high local rho2 expression was seen in the superficial grey layer of the superior colliculus, and in the dorsal lateral geniculate nucleus. Expression was also detected in the 6th layer of visual cortex and in the CA1 pyramidal cell layer of hippocampus. With reverse transcriptase-polymerase chain reaction, expression of rho1 was mainly seen in the adult rat retina and dorsal root ganglia, as well as, at a significantly lower level, in the superior colliculus, hippocampus, brain stem, thalamus, postnatal day 8 (P8) superior colliculus and P8 hippocampus. Expression pattern of rho3 mRNA was clearly different from that of rho1 and rho2, being strongest in the hippocampus, and significantly lower in the retina, dorsal root ganglia and cortex. No rho3 expression was observed in adult or P8 superior colliculus or in P8 hippocampus. The present results clearly demonstrate that expression of GABA receptor rho subunits is not restricted to the retina, but significant expression can also be detected in many other brain regions, especially in those belonging to the visual pathways. The expression pattern of the rho subunits may be helpful in solving the functional significance of the receptors formed from these subunits.

Animals↗
PubMed1998

Effect of heparin-binding growth-associated molecule (HB-GAM) on synaptic transmission and early LTP in rat hippocampal slices.

Heparin-binding growth-associated molecule (HB-GAM) is an 18-kDa developmentally regulated protein, which promotes neurite outgrowth, axonal guidance and synaptogenesis through interaction with cell-surface heparan-sulphate proteoglycans. We have studied the effect of HB-GAM on synaptic transmission and long-term potentiation (LTP) in the area CA1 of rat hippocampal slices, where HB-GAM mRNA is expressed in an activity-dependent manner. Injection of recombinant HB-GAM into the dendritic area inhibited tetanus-induced LTP without affecting baseline synaptic responses or the N-methyl-D-aspartate (NMDA)-receptor mediated transmission. HB-GAM did not depotentiate tetanus-induced LTP or prevent heterosynaptic LTP induced by application of tetraethylammonium (TEA), indicating that the effect was limited to early, synapse-specific stages of LTP induction. These results suggest that HB-GAM is involved in the regulation of synaptic plasticity in hippocampus.

Animals↗
PubMed1997

Long-lasting GABA-mediated depolarization evoked by high-frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network-driven, bicarbonate-dependent K+ transient.

Biphasic GABAA-mediated postsynaptic responses can be readily evoked in CA1 pyramidal neurons of rat hippocampal slices by high-frequency stimulus (HFS) trains in the presence of ionotropic glutamate receptor antagonists. In the present experiments with sharp microelectrodes, whole-cell techniques, and K+-selective microelectrodes, an HFS train (40 pulses at 100 Hz) applied in stratum radiatum close to the recording site evoked a brief hyperpolarizing IPSP (hIPSP), which turned into a prolonged (2-3 sec) depolarization (GABA-mediated depolarizing postsynaptic potential; GDPSP). The I-V relationships of the postsynaptic currents (hIPSC and GDPSC) had distinct characteristics: the hIPSC and the early GDPSC showed outward rectification, whereas the late GDPSC was reduced with positive voltage steps to zero or beyond (inward rectification), but often no clear reversal was seen. That two distinct currents contribute to the generation of the GDPSP was also evident from the finding that a second HFS train at peak or late GDPSP induced a prompt GABAA-mediated hyperpolarization. The GDPSP/C was dependent on the availability of bicarbonate, but not on interstitial or intrapyramidal carbonic anhydrase activity. The HFS train evoked a rapid GABAA-mediated bicarbonate-dependent increase in the extracellular K+ concentration ([K+]o), and the GDPSP followed the K+ transient in a sub-Nernstian manner. The spatial and pharmacological characteristics of the [K+]o shift indicated that it is generated by a local network of GABAergic interneurons. The brief ascending phase of the GDPSP is linked to a K+-dependent accumulation of intracellular Cl-. Thereafter, a nonsynaptic mechanism, a direct depolarizing effect of the [K+]o shift, is responsible for the most conspicuous characteristics of the GDPSP: its large amplitude and prolonged duration.

Animals↗
PubMed1997

Posttetanic excitation mediated by GABA(A) receptors in rat CA1 pyramidal neurons.

The contributions of gamma-aminobutyric acid (GABA) receptors to posttetanic excitation of CA1 pyramidal neurons in rat hippocampal slices were studied using extracellular and intracellular recording techniques. Synaptic responses were evoked on tetanic stimulation (100-200 Hz, 40-100 pulses) applied in stratum radiatum close (300-600 microm) to the recording site. Under control conditions, tetanic stimulation resulted in a triphasic depolarization/hyperpolarization/sustained depolarization sequence in area CA1 pyramidal cells. The late depolarization usually gave rise to a prolonged (< or = 3 s) spike firing. The late depolarization and the associated spike firing were blocked both specifically and completely (within a time window of 3-6 min starting from picrotoxin application) by the GABA(A) receptor antagonist picrotoxin (PiTX, 100 microM). Paradoxically, at this early stage of PiTX application, overall neuronal firing was attenuated to a higher degree than what was achieved by ionotropic glutamate antagonists. Complete block of ionotropic glutamate receptors by the antagonists D-2-amino-5-phosphonopentoate (AP5, 80 microM), 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX, 10 microM), and ketamine (50 microM) blocked the initial fast depolarization and suppressed the late one. Exposure to a permeable inhibitor of carbonic anhydrase, ethoxyzolamide (EZA, 50 microM) inhibited the late, apparently GABA-mediated depolarization. It is concluded that GABA can provide the main posttetanic excitatory drive in the adult hippocampus. The present results suggest that intense activation of GABAergic interneurons may accentuate the excitation of principal neurons and, hence, play an important facilitatory role in the induction of long-term potentiation (LTP) and epileptogenesis.

2-Amino-5-phosphonovalerate↗
PubMed1997

Ionic mechanisms of spontaneous GABAergic events in rat hippocampal slices exposed to 4-aminopyridine.

Ionic mechanisms of spontaneous GABAergic events in rat hippocampal slices exposed to 4-aminopyridine. J. Neurophysiol. 78: 2582-2591, 1997. Ion-selective (H+ and K+) microelectrode techniques as well as conventional extra- and intracellular recordings were used to study the ionic mechanisms of propagating spontaneous GABAergic events (SGEs) in rat hippocampal slices exposed to 4-aminopyridine (4-AP, 50-100 mu M). All experiments were made in the presence of antagonists of ionotropic glutamate receptors [10 mu M 6-nitro-7-sulphamoylbenzoquinoxaline-2,3-dione (NBQX) and 40 mu M -2-amino-5-phosphonopentanoic acid (AP5)]. The SGEs were composed of a negative-going change in field potential with a temporally coincident increase (0.7 +/- 0.3 mM; mean +/- SE) in extracellular K+ ([K+]o) and an alkaline transient (0.01-0.08 units) in extracellular pH (pHo) in stratum radiatum of the area CA1. Simultaneous intracellular recordings showed a triphasic hyperpolarization-depolarization-late hyperpolarization response in pyramidal cells. Application of pentobarbital sodium (PB, 100 mu M) decreased the interval between SGEs from a mean value of 35 to approximately 20 s and shortened the period of refractoriness of stimulus-evoked propagating events. This was accompanied by an increase in the amplitude of the field potential response of the [K+]o and the pHo shifts and of the depolarizing phase of the pyramidal-cell response. The SGEs were completely blocked by the gamma-aminobutyric acid-A (GABAA) receptor antagonist, picrotoxin (PiTX; 100 mu M). The amplitudes of the negative-going field potential and of the depolarizing phase of the pyramidal-cell response as well as the ionic shifts associated with SGEs were strongly suppressed in the nominal absence of CO2/HCO-3. There was a five-fold increase in the interevent interval, and propagating SGEs could not be evoked by stimuli given at intervals shorter than approximately 2-3 min. Exposure to inhibitors of carbonic anhydrase, benzolamide (BA; 10 micro M) or ethoxyzolamide (EZA; 50 mu M) fully blocked the alkaline pHo transients and turned them into acid shifts. The poorly membrane-permeant BA had no discernible effect on the other components of the SGEs, but application of EZA had effects reminiscent to those of CO2/HCO-3-free medium. Addition of the GABAA receptor-permeant weak-acid anion, formate (20 mM) reestablished the SGEs that were first suppressed by exposure to the CO2/HCO-3-free medium. No SGEs were seen in the presence of a similar concentration of the GABAA receptor-impermeant anion propionate. Unlike the alkaline transients associated with HCO-3-driven SGEs, those supported by formate were not blocked by BA. The present data suggest that an inward current carried by bicarbonate is necessary for the generation of SGEs and that the GABAA receptor-mediated excitatory coupling among GABAergic interneurons is essentially dependent on the availability of intracellular bicarbonate.

2-Amino-5-phosphonovalerate↗
PubMed1996

Optimal resource allocation for novelty detection in a human auditory memory.

A theory of resource allocation for neuronal low-level filtering is presented, based on an analysis of optimal resource allocation in simple environments. A quantitative prediction of the theory was verified in measurements of the magnetic mismatch response (MMR), an auditory event-related magnetic response of the human brain. The amplitude of the MMR was found to be directly proportional to the information conveyed by the stimulus. To the extent that the amplitude of the MMR can be used to measure resource usage by the auditory cortex, this finding supports our theory that, at least for early auditory processing, energy resources are used in proportion to the information content of incoming stimulus flow.

Acoustic Stimulation↗
PubMed1996

Acidosis of hippocampal neurones mediated by a plasmalemmal Ca2+/H+ pump.

Modulation of cytosolic calcium ([Ca2+]i) plays a key role in intracellular signalling. In neurones, intracellular Ca2+ transients are involved in the regulation of excitability as well as in synaptic transmission and plasticity. Here, we report that depolarization-induced elevation of [Ca2+]i evokes a prominent fall of intracellular pH (pHi) in voltage-clamped hippocampal pyramidal neurones dialysed with fluorescent indicators of H+ and Ca2+. This acidification is caused by exchange of internal calcium for extracellular protons via a vanadate- and eosin-sensitive plasmalemmal Ca2+/H+ pump. In view of the potent neuromodulatory actions of H+, these results raise the possibility that changes in excitability and synaptic plasticity, hitherto solely attributed to Ca2+ transients, may include a significant component mediated by pH shifts.

Acidosis↗
PubMed1996

The rho 1 GABA receptor cloned from rat retina is down-modulated by protons.

We have cloned and sequenced the full-length cDNA of the rat GABA (gamma-aminobutyric acid) rho 1 receptor subunit. The deduced amino acid sequence (474 amino acids) of the rat rho 1 receptor is 95% homologous to the previously cloned human rho 1 receptor. The rho 1 cDNA includes a 5' 129 bp and a 3' 2.6 kb untranslated region, which contains a sequence homologous to the human medium reiteration frequency repetitive sequence, MER18. The rat rho 1 receptor shows 45-50% similarity to the GABAA receptor beta subunits. This similarity is among the highest between all GABAA receptor subunit classes, giving no support at the molecular level to the classification of the rho subunits to a novel GABAC receptor class. The rat rho 1 cDNA formed functional GABA receptors insensitive to bicuculline, but sensitive to blockade by picrotoxin, when transiently expressed in the human embryonic kidney cell line HEK 293. We studied the sensitivity of the rho 1-mediated GABA current to variations in extracellular pH (pH0), and found that these receptors are strongly down-modulated by H+ ions. A decrease in pH0 from 7.4 to 6.4 decreased the GABA current by 51 +/- 8%, whereas an increase in pH0 from 7.4 to 8.4 increased the current by 77 +/- 8%. In view of the up-regulatory effect of protons on the GABA current observed in a number of preparations, the rho 1 receptors may contain a novel down-regulatory binding site for protons characteristic to these receptors.

Amino Acid Sequence↗
PubMed1996

Activity-induced enhancement of HB-GAM expression in rat hippocampal slices.

Heparin-binding growth-associated molecule (HB-GAM) is a developmentally regulated secretory protein with neurite outgrowth-promoting activity. High-frequency stimulation leading to induction of long-term potentiation (LTP) resulted in increased expression of HB-GAM in rat hippocampal area CA1. When tetanization was given in the presence of antagonists of the N-methyl-D-aspartate (NMDA) receptor and postsynaptic voltage-gated calcium channels, the mRNA level was comparable to control levels. The results indicate that high frequency stimulation inducing LTP results in calcium-dependent enhancement in HB-GAM expression, and imply a role for this extracellular protein in the modulation of synaptic function in the hippocampus.

Animals↗
PubMed1996

Effects of CO2 on excitatory transmission apparently caused by changes in intracellular pH in the rat hippocampal slice.

It is generally known that hyperventilation produces an increase in neuronal excitability. However, the mechanism whereby a change in CO2 partial pressure (PCO2) leads to changes in neural excitability is not known. We have studied this phenomenon in rat hippocampal slices using double-barrelled microelectrodes for simultaneous recording of field excitatory postsynaptic potentials (EPSPs) and extracellular pH in stratum radiatum of area CA1. A drop in PCO2 from the control level, 36 mmHg to 7 mmHg, produced an increase in extracellular pH of 0.4-0.6 pH units and a transient increase in EPSP slope by about 20-30%. Despite the stable extracellular alkalosis, the EPSP reverted back to its original level within 10 min. Switching back to 36 mmHg PCO2 restored the original extracellular pH and caused a transient decrease in the EPSP slope. Pharmacological blockade of NMDA receptor and/or GABAA receptor had no influence on the effects of CO2. An increase in PCO2 to 145 mmHg led to a stable fall in extracellular pH by 0.6 units and to a transient 30-50% decrease in EPSP slope. The above results indicate that the CO2-induced changes in neuronal excitability were not caused by changes in extracellular pH but they might have been mediated by changes in intracellular pH. Indeed, exposing the slices to the permeant weak base, trimethylamine (20 mM), which is known to produce a rise in intracellular pH, increased the EPSP slope by 50-70%. Application of 20 mM propionate (a permeant weak acid) decreased the EPSP slope by 40-60%. We conclude that the transient changes in the EPSP seen in response to changes in PCO2 are mediated by in intracellular pH.

2-Amino-5-phosphonovalerate↗
PubMed1996

Proton modulation of functionally distinct GABAA receptors in acutely isolated pyramidal neurons of rat hippocampus.

We have studied the effect of extracellular pH (pHo) on the GABAA receptor-mediated chloride conductance in acutely isolated pyramidal neurons from area CA1 of the rat hippocampus under whole-cell voltage clamp in bicarbonate-free solutions. The conductance evoked by saturating or near-saturating concentrations (200-1000 microM) of GABA showed a marked sensitivity to variations of pHo around 7.4. A decrease in pHo between 8.4 and 6.4 increased the GABAA receptor-mediated chloride conductance by about two-fold per pH unit. In contrast, when evoked by a low agonist concentration (1-10 microM) the conductance showed an equally marked decrease upon a decrease in pHo. The half-time for desensitization of the conductance induced by 500 microM GABA was around 900 ms at pHo 6.4 and 7.4, but decreased to 650 ms at pHo 8.4. A fall in pHo decreased the amount of desensitization of the conductance evoked by a 5 s application of 5 microM, but not of 500 microM, GABA. The concentration-response relationship of the GABA-induced conductance showed a local plateau between 50 and 100 microM of GABA, which was particularly evident at high pHo. Assuming two receptor populations with a high and a low affinity for GABA, the effect of H+ on the GABAA receptors could be explained as an increase in the EC50 of the high affinity receptor, and an apparently non-competitive potentiation of both the high and the low affinity receptors. The GABAA receptor-mediated conductance was markedly inhibited by 20-50 microM Zn2+. In addition, Zn2+ reverted the down-modulation by H+ observed at low GABA concentrations to up-modulation. Diazepam (1-10 microM) had only a marginal effect on the GABA-gated conductance. Taken together, the results suggest the coexistence in individual hippocampal neurons of two distinct GABAA receptor populations having differential sensitivities to H+. In the light of the inhibitory action of Zn2+ and the virtual absence of an effect of diazepam it is probable that a significant fraction of the GABAA receptors lack the gamma 2 subunit. The observation that an elevated pH has a strong suppressing effect on the conductance evoked by high concentrations of GABA may at least partly explain why an extracellular alkalosis leads to neuronal hyperexcitability.

Animals↗
PubMed1996

Redox modulation of calcium entry and release of intracellular calcium by thimerosal in GH4C1 pituitary cells.

In the present work we have investigated the actions of the oxidizing sulfhydryl reagent thimerosal on different mechanisms which regulate intracellular free Ca2+ concentration ([Ca2+]i) in GH4C1 pituitary cells. In intact Fura-2 loaded cells, low concentrations of thimerosal potentiated the spike phase of the TRH-induced (thyrotropin-releasing hormone) rise in [Ca2+]i, whereas high thimerosal concentrations inhibited it. The effect of thimerosal on the plateau phase was always inhibitory. The effect of thimerosal on the IP3-induced calcium release (IICR) was studied in permeabilized cells using the Ca2+ indicator Fluo-3. A low concentration of thimerosal (10 microM) stimulated IICR: the Ca2+ release induced by 300 nM inositol-1,4,5-trisphosphate (IP3) was enhanced in cells treated with thimerosal for 1 or 6 min (67 +/- 11 nM and 34 +/- 5 nM, respectively) as compared to control cells (17 +/- 2 nM). On the other hand, a high concentration of thimerosal (100 microM) inhibited IICR: when IP3 (10 microM) was added after a 5 min preincubation with thimerosal, the IP3-induced rise in [Ca2+]i (46 +/- 14 nM) was 57% smaller as compared with that seen in control cells (106 +/- 10 nM). The effect of thimerosal on the voltage-operated Ca2+ channels (VOCCs) was studied by depolarizing intact Fura-2 loaded cells by addition of 20 mM K+ to the cuvette. The depolarization-evoked increase in [Ca2+]i was inhibited in a dose-dependent manner by thimerosal. Direct evidence for an inhibitory effect of thimerosal on VOCCs was obtained by using the whole-cell configuration of the patch-clamp technique: thimerosal (100 microM) potently inhibited the Ba2+ currents through VOCCs. In addition, our results indicated that thimerosal inhibited the caffeine-induced increase in [Ca2+]i, and activated a capacitative Ca2+ entry pathway. The actions of thimerosal were apparently due to its oxidizing activity because the effects were mostly reversed by the thiol-reducing agent dithiothreitol (DTT). We conclude that, in GH4C1 pituitary cells, the mobilization of intracellular calcium and the different Ca2+ entry pathways are sensitive to redox modulation.

Animals↗
PubMed1996

Role of voltage-gated calcium channels in the generation of activity-induced extracellular pH transients in the rat hippocampal slice.

1. The role of voltage-gated calcium channels in the generation of activity-induced alkaline shifts in extracellular pH (pHo) was studied in rat hippocampal slices (area CAI) by means of Ca(2+)-and H(+)-selective microlectrodes inserted into the stratum pyramidale and/or stratum radiatum. 2. After complete pharmacological blockade of ionotropic glutamate receptors and gamma-aminobutyric acid-A (GABAA) receptors, trains (5-10 Hz, 5-10s) of antidromic spikes in pyramidal neurons were associated with a fast alkaline transient of up to 0.17 pH units and a fall in the extracellular Ca2+ concentration ([Ca2+]o). The alkaline shift was strongly enhanced upon inhibition of extracellular carbonic anhydrase. 3. Application of 100 microM Ni2+ plus 100 microM Cd2+ inhibited both the fall in [Ca2+]o and the alkaline transient triggered by antidromic spikes. The alkaline shift was abolished in the absence of extracellular Ca2+. 4. In the absence of postsynaptic receptor antagonists, alkaline transients linked to a given level of synaptic excitation in s. radiatum were strongly suppressed after blockade of somatic (and, consequently, of dendritic "backpropagating") spikes by microdrop application of tetrodotoxin to the cell-body layer. 5. We have previously shown that activity-induced alkaline transients in the CAI region are due to an influx of Ca2+ into neurons, which triggers an influx of H+ ions probably caused by activation of a plasmalemmal Ca2+/H+ ATPase. The present results indicate that much (in s. pyramidale perhaps all) of the pH-changing influx of Ca2+ is mediated by voltage-gated Ca2+ channels.

Action Potentials↗
PubMed1995

Studies on the role of metabotropic glutamate receptors in long-term potentiation: some methodological considerations.

There has been considerable interest recently in trying to elucidate the roles of metabotropic glutamate receptors (mGluRs) in the induction of long-term potentiation (LTP) in area CA1 of rat hippocampal slices. This has come about principally because of the development of specific mGluR agonists and antagonists. Recently we reported that the competitive mGluR antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) blocks the induction of LTP but not short-term potentiation (STP). We describe here the dose-dependency of the MCPG block; there is no effect at 100 microM while at 200 microM the block of LTP is normally complete but STP is spared. A higher concentration of MCPG (500 microM) has the same effect as 200 microM. We have also reported recently that high-frequency (tetanic) stimulation conditions a pathway such that MCPG fails to block the induction of subsequent LTP. We illustrate here that the conditioning effect of a tetanus lasts at least 6 h. We show how the pathway can be conditioned, without any persistent change in the synaptic response, by delivering tetanic stimulation in the presence of the specific NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (AP5). The pathway can subsequently be deconditioned by delivering low-frequency stimulation (900 shocks at 2 Hz) so that MCPG blocks the induction of subsequent LTP. We also have reported that the specific mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylate (ACPD) can induce LTP without the need for STP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗