Comparison of two piezoelectric cutting inserts for lateral bony window osteotomy: a retrospective study of 127 consecutive sites.

PURPOSE: The aim of the present retrospective clinical study was to compare the efficacy of two piezoelectric cutting inserts for the incidence, size, and types of sinus membrane perforations, and to evaluate their various advantages for lateral window osteotomy. MATERIALS AND METHODS: The study consisted of 127 maxillary sinus augmentation procedures performed at two centers. A bony window was made on the lateral wall of the maxillary sinus with either the piezoelectric saw or the round diamond insert and repositioned over the bone graft as a homologous bony barrier. The rate of membrane perforation during sinus augmentation between the two groups was compared and analyzed statistically by the chi-square test and the two-sample t test. RESULTS: Seven perforations were seen in the 127 maxillary sinus procedures in this study (5.51%). Six perforations in 84 cases (7.14%) occurred with the piezoelectric saw and one perforation in 43 sites (2.32%) occurred while using the round insert. No statistically significant difference was found between the rates of membrane perforation between the two inserts. CONCLUSION: The lateral bony window was created effectively with either of the two kinds of piezoelectric inserts. The membrane perforation rate was not significantly affected by the type of piezoelectric insert. The piezoelectric saw insert was more advantageous than the round diamond due to its greater precision and easier repositioning of the lateral bony window as a barrier.

Operant conditioning of rat navigation using electrical stimulation for directional cues and rewards.

Operant conditioning is often used to train a desired behavior in an animal. The contingency between a specific behavior and a reward is required for successful training. Here, we compared the effectiveness of two different mazes for training turning behaviors in response to directional cues in Sprague-Dawley rats. Forty-three rats were implanted with electrodes into the medial forebrain bundle and the left and right somatosensory cortices for reward and cues. Among them, thirteen rats discriminated between the left and right somatosensory stimulations to obtain rewards. They were trained to learn ipsilateral turning response to the stimulation of the left or right somatosensory cortex in either the T-maze (Group T) or the E| maze (Group W). Performance was measured by the navigation speed in the mazes. Performances of rats in Group T were enhanced faster than those in Group W. A significant correlation between performances during training and performance in final testing was observed in Group T starting with the fifth training session while such a correlation was not observed in Group W until the tenth training session. The training mazes did not however affect the performances in the final test. These results suggest that a simple maze is better than a complicated maze for training animals to learn directions and direct cortical stimulation can be used as a cue for direction training.

Piezoelectric internal sinus elevation (PISE) technique: a new method for internal sinus elevation.

This article reports the surgical procedure of a transalveolar approach for sinus floor elevation using piezoelectric surgery without a mallet, called piezoelectric internal sinus elevation (PISE) technique. PISE is the modified technique of the osteotome-mediated sinus floor elevation. Osteotome-mediated sinus floor elevation uses a mallet to break the sinus floor and to push sinus membrane up. Using this technique might possibly bring positional vertigo to the patient. PISE technique does not use a mallet during the procedure to break the sinus floor and to elevate the sinus membrane; therefore, it can reduce the possibility of postoperative positional vertigo.

Efficacy of demineralized bone matrix paste for maxillary sinus augmentation: a histologic and clinical study in humans.

OBJECTIVES: The aim of this study is to report the effect of paste type of demineralized bone matrix (DBM) on augmentation of maxillary sinus using clinical parameters. STUDY DESIGN: Sinus augmentation with DBM was performed on 5 maxillary sinuses. This study included 5 patients, 4 men and 1 woman, aged from 41 to 67 years (mean age 55 years). After an average of 6 months' healing period, a core bone was obtained and stained for histologic analysis. RESULTS: All implants showed favorable osseointegration, and final restorations were completed without failure in all cases. Histologically, new bone formation was active around grafted bone and grafted bone was well integrated to the newly formed bone matrix. In histomorphometric analysis, vital bone volume was 25.2 +/- 11.9%. CONCLUSION: The DBM paste is clinically useful for the increase of bone volume in sinus augmentation, because of its favorable effect of new bone formation and easy handling.

Cyclic AMP-mediated long-term facilitation of glycinergic transmission in developing spinal dorsal horn neurons.

cAMP is known to regulate neurotransmitter release via protein kinase A (PKA)-dependent and/or PKA-independent signal transduction pathways at a variety of central synapses. Here we report the cAMP-mediated long-lasting enhancement of glycinergic transmission in developing rat spinal substantia gelatinosa neurons. Forskolin, an adenylyl cyclase activator, elicited a long-lasting increase in the amplitude of nerve-evoked glycinergic inhibitory postsynaptic currents (IPSCs), accompanied by a long-lasting decrease in the paired-pulse ratio in immature substantia gelatinosa neurons, and this forskolin-induced increase in glycinergic IPSCs decreased with postnatal development. Forskolin also decreased the failure rate of glycinergic IPSCs evoked by minimal stimulation, and increased the frequency of glycinergic miniature IPSCs. All of these data suggest that forskolin induces the long-lasting enhancement of glycinergic transmission by increasing in the presynaptic release probability. This pre-synaptic action of forskolin was mediated by hyperpolarization and cyclic nucleotide-activated cation channels and an increase in intraterminal Ca(2+) concentration but independent of PKA. The present results suggest that cAMP-dependent signal transduction pathways represent a dynamic mechanism by which glycinergic IPSCs could potentially be modulated during postnatal development.

Reconstruction of atrophic anterior mandible using piezoelectric sandwich osteotomy: a case report.

Extensive loss of alveolar bone and teeth in the anterior mandible presents a complex problem for reconstruction. Numerous augmentation techniques are currently in use to create sufficient bone volume for reliable placement of endosseous implants in the case of severely resorbed mandibles. The aim of this report is to assess the efficacy of the piezoelectric sandwich osteotomy for vertical augmentation in the atrophic segment of anterior mandible through clinical and histologic studies. A complete osteotomized segment was made, using the piezoelectric saw, to make a segmented bone in the atrophic edentulous area and the mobile segment was elevated by 10-mm high vertically. Interpositional mineral allograft materials were inserted in the space between the basal bone and the segmented bone. A bone biopsy was performed on the augmented bone region and 3 dental implants were placed simultaneously 6 months later. About 10 mm of vertical gain was achieved by the sandwich technique. Histologic analysis presents new bone formation without inflammatory or foreign body reactions.

Differential pharmacological properties of GABAA receptors in axon terminals and soma of dentate gyrus granule cells.

Although it has been well established that GABA(A) receptors are molecular targets of a variety of allosteric modulators, such as benzodiazepines, the pharmacological properties of presynaptic GABA(A) receptors are poorly understood. In this study, the effects of diazepam and Zn(2+) on presynaptic GABA(A) receptors have been investigated by measuring the GABA(A) receptor-mediated facilitation of spontaneous glutamate release in mechanically dissociated rat CA3 pyramidal neurons. Diazepam significantly enhanced the muscimol-induced facilitation (particularly at submicromolar concentrations) of spontaneous glutamate release and shifted the concentration-response relationship for muscimol toward the left, whereas Zn(2+) (

Presynaptic glycine receptors facilitate spontaneous glutamate release onto hilar neurons in the rat hippocampus.

Although glycine receptors are found in most areas of the brain, including the hippocampus, their functional significance remains largely unknown. In the present study, we have investigated the role of presynaptic glycine receptors on excitatory nerve terminals in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs) were recorded in mechanically dissociated rat dentate hilar neurons attached with native presynaptic nerve terminals using a conventional whole-cell patch recording technique under voltage-clamp conditions. Exogenously applied glycine or taurine significantly increased the frequency of sEPSCs in a concentration-dependent manner. This facilitatory effect of glycine was blocked by 1 microM strychnine, a specific glycine receptor antagonist, but was not affected by 30 microM picrotoxin. In addition, Zn(2+) (10 microM) potentiated the glycine action on sEPSC frequency. Pharmacological data suggested that the activation of presynaptic glycine receptors directly depolarizes glutamatergic terminals resulting in the facilitation of spontaneous glutamate release. Bumetanide (10 microM), a specific Na-K-2C co-transporter blocker, gradually attenuated the glycine-induced sEPSC facilitation, suggesting that the depolarizing action of presynaptic glycine receptors was due to a higher intraterminal Cl(-) concentration. The present results suggest that presynaptic glycine receptors on excitatory nerve terminals might play an important role in the excitability of the dentate gyrus-hilus-CA3 network in physiological and/or pathological conditions.

Fungal infection as a complication of sinus bone grafting and implants: a case report.

Sinus bone grafts have been used successfully to augment atrophic posterior maxilla for dental implant placement. Even though sinus bone grafting is generally considered to be a safe surgical procedure, postoperative maxillary sinus infections can occur and therefore need to be considered. Bacteria, as well as viruses and fungi, have been identified as causative agents. Because fungal infection of the maxillary sinus after sinus bone grafting is not well known, we report a case of a middle-aged male patient along with the clinical, radiographic, and histologic findings. The patient was referred from his private dentist because of failed sinus bone grafting and osseointegration of implants. The surgical approach to the sinus yielded a friable mass of brownish-red material from the sinus. Review of pathology slides revealed a noninvasive hyphal mass caused by Aspergillus and polypous mucosa. After surgical removal of the mycotic masses, sinus bone grafting, using allograft, was performed. Bone formation after the healing period was favorable and dental implants were placed. There was no recurrence of fungal sinusitis.

Zinc modulation of glycine receptors in acutely isolated rat CA3 neurons.

Glycine and GABA are the primary inhibitory neurotransmitters in the spinal cord and brain stem, with glycine exerting its physiological roles by activating strychnine-sensitive ionotropic receptors. Glycine receptors are also expressed in the brain, including the cortex and hippocampus, but their physiological roles and pharmacological properties are largely unknown. Here, we report the pharmacological properties of functional glycine receptors in acutely isolated rat CA3 neurons using conventional whole-cell patch clamp techniques. Both glycine and taurine, which are endogenous agonists of glycine receptors, elicited Cl(-) currents in a concentration-dependent manner. The glycine-induced current (I(Gly)) was inhibited by strychnine, picrotoxin or cyclothiazide in a concentration-dependent manner. At lower concentrations (0.01-1 microM), ICS-205,930 potentiated I(Gly), but at higher concentrations (>10 microM) it inhibited I(Gly). These pharmacological properties strongly suggest that CA3 neurons express functional strychnine-sensitive glycine receptors containing alpha2 subunits. Furthermore, at lower concentrations (1-30 microM), Zn(2+) potentiated I(Gly), but at higher concentrations (>100 microM) it inhibited I(Gly). Considering that Zn(2+) is synaptically co-released with glutamate from mossy fiber terminals that make excitatory synapses onto CA3 neurons, these results suggest that endogenous Zn(2+) modulation of these glycine receptors may have an important role in the excitability of CA3 neurons.

Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-kappaB.

In the present study, we investigated the neurotoxicity of bisphenol A [BPA; 2,2-bis-(4 hydroxyphenyl) propane] and the underlying mechanisms of action in mouse hippocampal HT-22 cells. BPA, known to be a xenoestrogen, is used in the production of water bottles, cans, and teeth suture materials. BPA-treated HT-22 cells showed lower cell viability than did controls at concentrations of BPA over 100 microM. BPA induced apoptotic cell death as indicated by staining with Hoechst 33258, costaining with Annexin V/propidium iodide, and activation of caspase 3. BPA regulated the generation of reactive oxygen species (ROS) by increasing intracellular calcium. BPA activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor (NF)-kappaB. Pretreatment with specific inhibitors for calcium, ROS, ERK, and JNK decreased BPA-induced cell death; however, inhibitor for NF-kappaB increased BPA-induced cell death. The results suggest that calcium, ROS, ERK, and JNK are involved in BPA-induced apoptotic cell death in HT-22 cells. In contrast, an NF-kappaB cascade was activated for survival signaling after BPA treatment.

Adenosine A1 receptors inhibit GABAergic transmission in rat tuberomammillary nucleus neurons.

The adenosinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) was investigated in mechanically dissociated rat tuberomammillary nucleus (TMN) neurons using a conventional whole-cell patch clamp technique. Adenosine (100 microM) reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that adenosine acts presynaptically to decrease the probability of spontaneous GABA release. The adenosine action on GABAergic mIPSC frequency was completely blocked by 1 microM DPCPX, a selective A(1) receptor antagonist, and mimicked by 1 microM CPA, a selective A(1) receptor agonist. This suggests that presynaptic A(1) receptors were responsible for the adenosine-mediated inhibition of GABAergic mIPSC frequency. CPA still decreased GABAergic mIPSC frequency even either in the presence of 200 microM Cd(2+), a general voltage-dependent Ca(2+) channel blocker, or in the Ca(2+)-free external solution. However, the inhibitory effect of CPA on GABAergic mIPSC frequency was completely occluded by 1 mM Ba(2+), a G-protein coupled inwardly rectifying K(+) (GIRK) channel blocker. In addition, the CPA-induced decrease in mIPSC frequency was completely occluded by either 100 microM SQ22536, an adenylyl cyclase (AC) inhibitor, or 1 muM KT5720, a specific protein kinase A (PKA) inhibitor. The results suggest that the activation of presynaptic A(1) receptors decreases spontaneous GABAergic transmission onto TMN neurons via the modulation of GIRK channels as well as the AC/cAMP/PKA signal transduction pathway. This adenosine A(1) receptor-mediated modulation of GABAergic transmission onto TMN neurons may play an important role in the fine modulation of the excitability of TMN histaminergic neurons as well as the regulation of sleep-wakefulness.

Effects of carbamazepine and amitriptyline on tetrodotoxinresistant Na+ channels in immature rat trigeminal ganglion neurons.

Although anticonvulsant drugs that block voltage-dependent Na+ channels have been widely used for neuropathic pain, including peripheral nerve injury-induced pain, much less is known about the actions of these drugs on immature trigeminal ganglion (TG) neurons. Here we report the effects of carbamazepine (CBZ) and amitriptyline (ATL) on tetrodotoxin-resistant (TTX-R) Na' channels expressed on immature rat TG neurons. TTX-R Na+ currents (I(Na)) were recorded in the presence of 300 nM TTX by use of a conventional whole-cell patch clamp method. Both CBZ and ATL inhibited TTX-R I(Na) in a concentration-dependent manner, but ATL was more potent. While CBZ and ATL did not affect the overall voltage-activation relationship of TTX-R Na+ channels, both drugs shifted the voltage-activation relationship to the left, indicating that they inhibited TTX-R Na+ channels more efficiently at depolarized membrane potentials. ATL showed a profound use-dependent blockade of TTX-R I(Na), but CBZ had little effect. The present results suggest that both CBZ and ATL, common drugs used for treating neuropathic pain, efficiently inhibit TTX-R Na+ channels expressed on immature TG neurons, and that these drugs might be useful for the treatment of trigeminal nerve injury-induced neuropathic pain, as well as the inhibition of ongoing central sensitization, even during immature periods.

GABA(B) receptor-mediated presynaptic inhibition of glycinergic transmission onto substantia gelatinosa neurons in the rat spinal cord.

The GABA(B) receptor-mediated presynaptic inhibition of glycinergic transmission was studied from young rat substantia gelatinosa (SG) neurons using a conventional whole-cell patch clamp technique. Action potential-dependent glycinergic inhibitory postsynaptic currents (IPSCs) were recorded from SG neurons in the presence of 3 mM kynurenic acid and 10 microM SR95531. In these conditions, baclofen (30 microM), a selective GABA(B) receptor agonist, greatly reduced the amplitude of glycinergic IPSCs and increased the paired-pulse ratio. Such effects were completely blocked by 3 microM CGP55845, a selective GABA(B) receptor antagonist, indicating that the activation of presynaptic GABA(B) receptors decreases glycinergic synaptic transmission. Glycinergic IPSCs were largely dependent on Ca2+ influxes passing through presynaptic N- and P/Q-type Ca2+ channels, and these channels contributed equally to the baclofen-induced inhibition of glycinergic IPSCs. However, the baclofen-induced inhibition of glycinergic IPSCs was not affected by either 100 microM SQ22536, an adenylyl cyclase inhibitor, or 1 mM Ba2+, a G-protein coupled inwardly rectifying K+ channel blocker. During the train stimulation (10 pulses at 20 Hz), which caused a marked synaptic depression of glycinergic IPSCs, baclofen at a 30 microM concentration completely blocked glycinergic synaptic depression, but at a 3 microM concentration it largely preserved glycinergic synaptic depression. Such GABA(B) receptor-mediated dynamic changes in short-term synaptic plasticity of glycinergic transmission onto SG neurons might contribute to the central processing of sensory signals.

Alpha neurofeedback improves the maintaining ability of alpha activity.

The effects of alpha-neurofeedback (ANF) on electroencephalographic alpha-activity were investigated. Each session consisted of a 2.5-min eye-opened state and 17.5-min of ANF, which was divided into 16 1.25-min bins. Alpha amplitudes were gradually increased as the session was repeated. The maximum value at the start of ANF gradually decreased as time passed, but the slowdown of alpha-activity during each session was decreased as the session was repeated. The correlation between alpha-activity at the end of ANF and at the following session's eye-opened state was highly significant. These results showed that ANF enhances the ability of alpha-activity to maintain itself rather than the increase of alpha-amplitude during intrasession and that the maintained alpha-activity during former training remained until the next session.

Effects of a cell adhesion molecule coating on the blasted surface of titanium implants on bone healing in the rabbit femur.

PURPOSE: One strategy to improve implant osseointegration is to control the quality of the bone reaction at the implant-bone tissue interface using an implant coated with biologically active substances. The purpose of this study was to investigate the effect of a tetra-cell adhesion molecule (T-CAM) coating composed of 4 cell-adhesion molecules-an arginine-glycine-aspartic acid (RGD) sequence, a proline-histidine-serine-arginine-asparagine (PHSRN) sequence, a tyrosine-histidine sequence (YH), and a glutamic acid-proline-aspartic acid-isoleucine-methionine (EPDIM)-on the rough-surfaced titanium implant on peri-implant bone formation in the rabbit femur with poor local bone conditions and minimal primary stability. MATERIALS AND METHODS: Seven T-CAM-coated (blasted/T-CAM) and uncoated (blasted) implants with a rough surface (hydroxyapatite-blasted; Ra = 1.8 microm) were placed in slightly oversized beds of the metaphyses of the right and left femurs of 7 New Zealand White rabbits with light tactile pressure, and minimal primary stability was obtained. To evaluate the effects of T-CAM coating on the peri-implant bone healing response, histomorphometric analysis was performed 8 weeks after surgery. The 2 groups were compared using the Student t test, with a significance level of P < .05. RESULTS: Compared to uncoated blasted implants at 8 weeks of healing, the blasted/T-CAM implants showed a significantly greater amount of bone-implant contact (BIC; P < .01) and new bone formation in the zones 0 to 100 microm and 0 to 500 microm lateral to the implant surface (P < .05) in the medullary space. CONCLUSION: The T-CAM coating on the rough-surfaced titanium implants significantly enhanced peri-implant bone formation in rabbit femurs with poor local bone condition.

Serotoninergic modulation of GABAergic synaptic transmission in developing rat CA3 pyramidal neurons.

Serotoninergic modulation of GABAergic mIPSCs was investigated in immature (postnatal 12-16-days old) rat CA3 pyramidal neurons using a conventional whole-cell patch clamp technique. Serotonin or 5-hydroxytryptamine (5-HT) (10 micromol/L) transiently and explosively increased mIPSC frequency with a small increase in the current amplitude. However, 5-HT did not affect the GABA-induced postsynaptic currents, indicating that 5-HT acts presynaptically to facilitate the probability of spontaneous GABA release. The 5-HT action on GABAergic mIPSC frequency was completely blocked by 100 nmol/L MDL72222, a selective 5-HT(3) receptor antagonist, and mimicked by mCPBG, a selective 5-HT(3) receptor agonist. The 5-HT action on GABAergic mIPSC frequency was completely occluded either in the presence of 200 mumol/L Cd2+ or in the Na+-free external solution, suggesting that the 5-HT(3) receptor-mediated facilitation of mIPSC frequency requires a Ca2+ influx passing through voltage-dependent Ca2+ channels from the extracellular space, and that presynaptic 5-HT(3) receptors are less permeable to Ca2+. The 5-HT action on mIPSC frequency in the absence or presence of extracellular Na+ gradually increased with postnatal development. Such a developmental change in the 5-HT(3) receptor-mediated facilitation of GABAergic transmission would play important roles in the regulation of excitability as well as development in CA3 pyramidal neurons.

Multiple effects of bisphenol A, an endocrine disrupter, on GABA(A) receptors in acutely dissociated rat CA3 pyramidal neurons.

Bisphenol A (BPA), an endocrine disrupter, is contained in cans, polycarbonate bottles and some dental sealants. While the toxicological effects of BPA on the endocrine system have been extensively studied, its action on the central nervous system is poorly understood. Herein, we report the effects of BPA on GABA-induced currents (I(GABA)), using a conventional whole-cell patch clamp technique from acutely isolated rat CA3 pyramidal neurons. By itself, BPA concentration-dependently elicited the membrane current, which was significantly blocked by bicuculline, a selective GABA(A) receptor antagonist. BPA potentiated the peak I(GABA) induced by lower concentrations of GABA (<10 microM) in a concentration-dependent manner. The extent of BPA-induced potentiation of I(GABA) was significantly reduced by either diazepam or ethanol, allosteric modulators of GABA(A) receptors. BPA, however, inhibited the peak I(GABA) induced by higher concentrations of GABA (>30 microM), and accelerated the desensitization rate of I(GABA). BPA also greatly inhibited the steady state I(GABA) induced by higher concentrations of GABA (>30 microM) in a noncompetitive manner. In addition, BPA affected synaptic GABA(A) receptors as it decreased the amplitude of GABAergic miniature inhibitory postsynaptic currents in a concentration-dependent manner. Considering its complex modulatory effects on GABA(A) receptors, BPA might have potential toxicological effects on the central nervous system.

Effects of a novel calcium titanate coating on the osseointegration of blasted endosseous implants in rabbit tibiae.

OBJECTIVE: The purpose of this study was to investigate the effects of a nanostructured calcium coating on the surfaces of blasted Ti implants on peri-implant bone formation in the rabbit tibiae. MATERIAL AND METHODS: Threaded implants (3.75 mm in diameter, 6 mm in length) were roughened by hydroxyapatite (HA) blasting (control; blasted implants). The implants were then hydrothermally treated in a Ca-containing solution for 24 h to prepare Ca-incorporated Ti surfaces (experimental; blasted/Ca implants). Surface characterizations were performed by scanning electron microscopy and stylus profilometry before and after Ca coating. Forty-two implants (21 control and 21 experimental) were placed in the proximal tibiae of seven New Zealand White rabbits. Each rabbit received six implants. To evaluate the effects of the nanostructured Ca coating on the peri-implant bone-healing response, removal torque tests and histomorphometric analyses were performed 6 weeks after surgery. RESULTS: The Ca coating did not significantly change the surface properties produced by blasting at the micron level. Histologically, active bone apposition was observed in the blasted/Ca implants in the marrow space. Compared with the blasted implants, the blasted/Ca implants showed significantly increased bone-to-implant contact over the total implant length (P<0.01) and greater mean removal torque values (P<0.05). DISCUSSION AND CONCLUSION: The nanostructured, Ca-incorporated surface significantly enhanced the peri-implant bone-healing response of HA-blasted Ti implants. It may be concluded that the use of nanostructured, Ca-coated surfaces may have synergic effects in enhancing osseointegration of blasted Ti implants due to their micron-scaled surface properties and biologically active surface chemistry.

The Na(+)/H(+) exchanger is a major pH regulator in GABAergic presynaptic nerve terminals synapsing onto rat CA3 pyramidal neurons.

The effects of pH(i) on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were studied in mechanically dissociated CA3 pyramidal neurons, by use of ammonium prepulse and whole-cell patch-clamp techniques, under the voltage-clamp condition. NH(4)Cl itself, which is expected to alkalinize pH(i), increased GABAergic mIPSC frequency in a concentration-dependent manner. In contrast, NH(4)Cl decreased mIPSC frequency, either in the presence of 200 microm Cd(2+) or in Ca(2+)-free external solution, suggesting that intraterminal alkalosis decreased GABAergic mIPSC frequency while [NH4(+)] itself may activate Ca(2+) channels by depolarizing the terminal. On the other hand, GABAergic mIPSC frequency was greatly increased immediately after NH(4)Cl removal, a condition expected to acidify pH(i), and recovered to the control level within 2 min after NH(4)Cl removal. This explosive increase in mIPSC frequency observed after NH(4)Cl removal was completely eliminated after depletion of Ca(2+) stores with 1 microm thapsigargin in the Ca(2+)-free external solution, suggesting that acidification increases in intraterminal Ca(2+) concentration via both extracellular Ca(2+) influx and Ca(2+) release from the stores. However, the acidification-induced increase in mIPSC frequency had not recovered by 10 min after NH(4)Cl removal either in the Na(+)-free external solution or in the presence of 10 microm 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), a specific Na(+)/H(+) exchanger (NHE) blocker. The present results suggest that NHEs are major intraterminal pH regulators on GABAergic presynaptic nerve terminals, and that the NHE-mediated regulation of pH(i) under normal physiological or pathological conditions might play an important role in the neuronal excitability by increasing inhibitory tones.