Toshitaka Yamaga

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (9)18.67 Total impact

  • Masahito Wakita · Naoki Kotani · Toshitaka Yamaga · Norio Akaike ·
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    ABSTRACT: We evaluated the effects of N2O on synaptic transmission using a preparation of mechanically dissociated rat hippocampal CA3 neurons that allowed assays of single bouton responses evoked from native functional nerve endings. We studied the effects of N2O on GABAA, glutamate, AMPA and NMDA receptor-mediated currents (IGABA, IGlu, IAMPA and INMDA) elicited by exogenous application of GABA, glutamate, (S)-AMPA, and NMDA and spontaneous, miniature, and evoked GABAergic inhibitory and glutamatergic excitatory postsynaptic current (sIPSC, mIPSC, eIPSC, sEPSC, mEPSC and eEPSC) in mechanically dissociated CA3 neurons. eIPSC and eEPSC were evoked by focal electrical stimulation of a single bouton. Administration of 70% N2O altered neither IGABA nor the frequency and amplitude of both sIPSCs and mIPSCs. In contrast, N2O decreased the amplitude of eIPSCs, while increasing failure rates (Rf) and paired-pulse ratios (PPR) in a concentration-dependent manner. On the other hand, N2O decreased IGlu, IAMPA and INMDA. Again N2O did not change the frequency and amplitude of either sEPSCs of mEPSCs. N2O also decreased amplitudes of eEPSCs with increased Rf and PPR. The decay phases of all synaptic responses were unchanged. The present results indicated that N2O inhibits the activation of AMPA/KA and NMDA receptors and also that N2O preferentially depress the action potential-dependent GABA and glutamate releases but had little effects on spontaneous and miniature releases.
    Brain research bulletin 09/2015; 118. DOI:10.1016/j.brainresbull.2015.09.001 · 2.72 Impact Factor
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    ABSTRACT: The effects of heavy water (deuterium oxide, D2O) on GABAergic and glutamatergic spontaneous and evoked synaptic transmission were investigated in acute brain slice and isolated 'synaptic bouton' preparations of rat hippocampal CA3 neurons. The substitution of D2O for H2O reduced the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner, but had no effect on glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs). In contrast, for evoked synaptic responses in isolated neurons, the amplitude of both inhibitory and excitatory postsynaptic currents (eIPSCs and eEPSCs) was decreased in a concentration-dependent manner. This was associated with increases of synaptic failure rate (Rf) and paired-pulse ratio (PPR). The effect was larger for eIPSCs as compared to eEPSCs. These results clearly indicate that D2O acts differently on inhibitory and excitatory neurotransmitter release machinery. Furthermore, D2O significantly suppressed GABAA receptor-mediated whole-cell current (IGABA), but did not affect glutamate receptor-mediated whole-cell current (IGlu). The combined effects of D2O at both the pre- and postsynaptic sites may explain the greater inhibition of eIPSCs as compared to eEPSCs. Finally, D2O did not enhance or otherwise affect the actions of general anesthetics, nitrous oxide and propofol on spontaneous or evoked GABAergic and glutamatergic neurotransmissions, nor on IGABA and IGlu. Our results suggest that previously reported effects of D2O to mimic and/or modulate anesthesia potency result from mechanisms other than modulation of GABAergic and glutamatergic neurotransmission. Copyright © 2014, Journal of Neurophysiology.
    Journal of Neurophysiology 05/2015; 114(2):jn.00801.2014. DOI:10.1152/jn.00801.2014 · 2.89 Impact Factor
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    ABSTRACT: Atrial and brain natriuretic peptides (ANP and BNP) exist in the central nervous system and modulate neuronal function, although the locus of actions and physiological mechanisms are still unclear. In the present study we used rat spinal sacral dorsal commissural nucleus (SDCN) and hippocampal 'synaptic bouton' preparations, to record both spontaneous and evoked glycinergic inhibitory postsynaptic currents (sIPSCs and eIPSCs) in SDCN neurons, and the evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA3 neurons. ANP potently and significantly reduced the sIPSC frequency without affecting the sIPSC mean amplitude. ANP also potently reduced the amplitude of eIPSCs concurrently increasing the failure rate and the paired pulse ratio response. These ANP actions were blocked by anantin, a specific type A natriuretic peptide receptor (NPR-A) antagonist. The results clearly indicate that ANP acts directly on glycinergic presynaptic nerve terminals to inhibit glycine release via presynaptic NPR-A. The ANP effects were not blocked by the membrane permeable cGMP analogue (8Br-cGMP) suggesting a transduction mechanisms not simply related to increasing cGMP levels in nerve terminals. BNP did not affect on glycinergic sIPSCs and eIPSCs. Moreover, both ANP and BNP had no effect on glutamatergic EPSCs in hippocampal CA3 neurons. The results indicate a potent and selective presynaptic inhibitory action of ANP on glycinergic transmission in spinal cord sensory circuits.
    Brain research bulletin 09/2013; 99. DOI:10.1016/j.brainresbull.2013.09.003 · 2.72 Impact Factor
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    ABSTRACT: The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented "Nukazuke" and "Kasuzuke" ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I(Na)) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in "Nukazuke" and "Kasuzuke" ovaries decreased to 1/50-1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes" fresh muscle that is normally eaten. It was concluded that the fermented "Nukazuke" and "Kasuzuke" ovaries of puffer fish T. Stictonotus are safe and harmless as food.
    Toxins 01/2013; 5(1):193-202. DOI:10.3390/toxins5010193 · 2.94 Impact Factor
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    ABSTRACT: We observed the effects of tetanus toxin (TeNT) on spontaneous miniature and evoked postsynaptic currents at inhibitory (glycinergic) and excitatory (glutamatergic) synapses in SDCN of rat spinal cord, by use of 'synaptic bouton' preparations, under voltage clamp condition. TeNT (>10 pM) dose-dependently decreased the frequency without affecting amplitude of glycinergic spontaneous miniature IPSCs. However, TeNT (100 pM) had no effect on frequency or amplitude of glutamatergic spontaneous EPSCs. Focal paired electrical stimulation of 'synaptic boutons' elicited two consecutive glycinergic eIPSCs or glutamatergic eEPSCs with large amplitude and low failure rate (Rf). TeNT (100 pM) reduced the amplitude and increased the failure rate of the first glycinergic eIPSCs and greatly enhanced the ratio of the second to first (P2/P1) eIPSCs. Application of 4-AP restored glycinergic eIPSCs suppressed by TeNT (100 pM). However, TeNT (100 pM) had no effect on the amplitude, Rf or P2/P1 ratio of glutamatergic eEPSCs. These results show that TeNT pre-synaptically affects spontaneous and evoked, and inhibitory and excitatory neurotransmitter release differentially, thereby suggesting that molecular events underlying spontaneous and evoked, inhibitory and excitatory neurotransmitter release may be different in CNS, and that the release machinery becomes less sensitive to Ca²⁺ in TeNT poisoned 'synaptic boutons'.
    Toxicon 03/2012; 59(3):385-92. DOI:10.1016/j.toxicon.2011.12.009 · 2.49 Impact Factor
  • Toshitaka Yamaga · Shuji Aou · Min-Chul Shin · Masahito Wakita · Norio Akaike ·
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    ABSTRACT: Our recent study showed a possibility that newly developed A2 type botulinum toxin (A2NTX) inhibits both spontaneous and evoked transmitter release from inhibitory (glycinergic or GABAergic) and excitatory (glutamatergic) nerve terminals using rat spinal sacral dorsal commissural nucleus neurons. In the present study, to determine the modulatory effect of A2NTX on glycinergic and glutamatergic release probabilities, we tested the effects of A2NTX on a single inhibitory or excitatory nerve ending adherent to a dissociated neuron that was activated by paired-pulse stimuli by using the focal electrical stimulation technique. The results of the present paired-pulse experiments showed clearly that A2NTX enhanced paired-pulse facilitation of evoked glycinergic inhibitory postsynaptic currents and glutamatergic excitatory postsynaptic currents and increased the failure rate (Rf) of the first postsynaptic currents (P(1)) and both the responses. These effects of A2NTX on the amplitude and Rf of the P(1) and the second postsynaptic currents (P(2)) and paired-pulse ratio were rescued by application of 4-aminophthalimide. In summary, the present results showed that A2NTX acts purely presynaptically and inhibits the release machinery of transmitters such as glycine and glutamate, and the transmitter release machinery became less sensitive to intracellular free-Ca(2+) in A2NTX poisoned nerve terminals.
    Journal of Pharmacological Sciences 12/2011; 118(1):75-81. DOI:10.1254/jphs.11124FP · 2.36 Impact Factor
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    ABSTRACT: Recent studies have demonstrated that the botulinum neurotoxins inhibit the release of acetylcholine, glutamate, GABA, and glycine in central nerve system (CNS) neurons. The Na(+) current (I(Na)) is of major interest because it acts as the trigger for many cellular functions such as transmission, secretion, contraction, and sensation. Thus, these observations raise the possibility that A type neurotoxin might also alter the I(Na) of neuronal excitable membrane. To test our idea, we examined the effects of A type neurotoxins on I(Na) of central and peripheral neurons. The neurotoxins in femtomolar to picomolar concentrations produced substantial decreases of the neuronal I(Na), but interestingly the current inhibition was saturated at about maximum 50% level of control I(Na). The inhibitory pattern in the concentration-response curve for the neurotoxins differed from tetrodotoxin (TTX), local anesthetic, and antiepileptic drugs that completely inhibited I(Na) in a concentration-dependent manner. We concluded that A type neurotoxins inhibited membrane Na(+)-channel activity in CNS neurons and that I(Na) of both TTX-sensitive and -insensitive peripheral dorsal ganglion cells were also inhibited similarly to a maximum 40% of the control by the neurotoxins. The results suggest evidently that A2NTX could be also used as a powerful drug in treating epilepsy and several types of pain.
    Journal of Pharmacological Sciences 12/2011; 118(1):33-42. DOI:10.1254/jphs.11060FP · 2.36 Impact Factor
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    ABSTRACT: We performed a comparative study on the effects of toxin extracts prepared from muscle and liver of two different puffer fishes on voltage dependent sodium current (I(Na)), and compared the results with that of tetrodotoxin (TTX). The amount of toxin contained in the muscle or liver expressed as an amount of equipotent TTX differed in the two species (0.11-57.98 microg TTX/g tissue). In addition, we observed the effects of TTX or toxin extracts on the twitch contraction evoked by direct muscle stimulation of the rat hemidiaphragm or indirect phrenic nerve stimulations, in an attempt to understand the mechanisms involved in the transmission failure in the respiratory muscles, due to the ingestion of TTX bearing puffers, and found that TTX or toxin extracts preferentially affect motor nerve rather than muscle.
    Fukuoka igaku zasshi = Hukuoka acta medica 08/2010; 101(8):173-81.
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    ABSTRACT: The action of ginkgolide B (GB), a powerful compound of Ginkgo biloba extract, on glycine-mediated spontaneous currents in rat spinal sacral dorsal commissural nucleus (SDCN) neurons was examined. IPSCs evoked in spinal cord slices were inhibited in a dose-dependent manner by the addition of GB to the superfusion solution. The amplitude of eIPSCs was reduced to 61 ± 6.4% by 10 μM GB with acceleration of the kinetics of the currents, indicating the effect of GB on channel pores. Both the amplitude and success ratio (Rsuc) of eIPSC induced by electrical focal stimulation of single glycinergic nerve endings (boutons) also changed in the presence of 1 μM GB. These data suggest that GB modulates not only post-synaptic glycine receptors but also the pre-synaptic glycine release machinery.
    Neurophysiology 08/2009; 41(4):250-257. DOI:10.1007/s11062-010-9104-1 · 0.20 Impact Factor

Publication Stats

15 Citations
18.67 Total Impact Points


  • 2009-2015
    • Kumamoto University
      • Graduate School of Science and Technology
      Kumamoto, Kumamoto, Japan
  • 2011
    • Kyushu Institute of Technology
      • Department of Brain Sciences & Engineering
      Kitakyūshū, Fukuoka, Japan
  • 2010
    • Kyushu University
      • Graduate School of Medical Sciences
      Fukuoka-shi, Fukuoka-ken, Japan