• Title/Summary/Keyword: $K_{Ca}$ channels

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Isolation and Electrical Characterization of the Rat Spinal Dorsal Horn Neurons (랫드 척수후각 단일세포 분리 및 특성에 관한 연구)

  • Han, Seong-Kyu;Ryu, Pan-Dong
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.283-292
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    • 1996
  • The spinal dorsal horn is the area where primary afferent fibers terminate and cutaneous sensory information is processed. A number of putative neurotransmitter substances, including excitatory and inhibitory amino acids and peptides, are present in this region. In this study, single neurons of the spinal dorsal horn were acutely isolated and the properties of whole cell current and responses to excitatory and inhibitory neurotransmitters were studied by patch clamp technique. Transverse slice ($(300{\mu}m$) of lumbar spinal cords from young rats$(7{\sim}14\;days)$ were sequentially treated with two pretenses(pronase 0.75 mg/ml and thermolysin 0.75 mg/ml), then single neurons were mechanically dissociated. These neurons showed near-intact morphology such as multipolar, ellipsoidal and bipolar, and pyramidal cells and we recorded the typical whole cell currents of $K^+$, $Ca^{2+}$ and ligand-operated channels from these neurons. Glutamate $(30{\mu}M)$ and N-methyl-D-aspartate(NMDA, $30{\mu}M)$ induced inward currents of $117{\pm}12.4$ pA(n=5) and $49{\pm}6.9$ pA(n=3), respectively. Glycine $(1{\mu}M)$ potentiated glutamate-induced currents $4{\sim}5$ times and NMDA-induced currents $8{\sim}10$ times. In addition, glycine $(30{\mu}M)$ induced Inward current ($31{\pm}6.1$ nA, n=2), which was rapidly desensitized after the peak to a new steady-state level. However, the inward currents induced by ${\gamma}-amino$ butyric acid(GABA, $1{\mu}M$) decreased continuously after the peak($226{\pm}41.6$ pA, n=3) under the similar experimental condition. The ionic currents and pharmacological responses of isolated neurons in this work were similar to those observed in vivo or in vitro spinal cord slice, indicating that acutely isolated neurons could be effectively used for further pharmacological studies.

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Geochemical Characteristics of Stream Sediments Based on Bed Rocks in the Naju Area, Korea (기반암에 따른 나주지역 하상퇴적물의 지구화학적 특성)

  • Park, Young-Seog;Kim, Jong-Kyun;Jung, Young-Hwa
    • Journal of the Korean earth science society
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    • v.27 no.1
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    • pp.49-60
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    • 2006
  • The purpose of this study is to investigate geochemical characteristics for stream sediments in the Naju area. We collected 139 stream sediments samples from primary channels. Samples were dried slowly in the laboratory and chemical analysis was carried out using XRF. ICP-AES and NAA. In order to investigate geochemical characteristics, the geological groups categorized into granitic gneiss area, schist area, granite area, arenaceous rock area, tuff area, andesite area, and rhyolite area. Average contents of major elements for geological groups are $SiO_2\;58.37{\sim}66.06wt.%,\;Al_2O_3\;13.98{\sim}18.41wt.%,\;Fe_2O_3\;4.09{\sim}6.10wt.%,\;CaO\;0.54{\sim}1.33wt.%,\;MgO\;0.86{\sim}1.34wt.%,\;K_2O\;2.38{\sim}4.01wt.%,\;Na_2O\;0.90{\sim}1.32wt.%,\;TiO_2\;0.82{\sim}1.03wt.%,\;MnO\;0.09{\sim}0.15wt.%,\;P_2O_5\;0.11{\sim}0.18wt.%$. According to the comparison of average contents of major elements, $Al_2O_3\;and\;K_2O$ are higher in granitic gneiss area, $Fe_2O_3,\;CaO,\;P_2O_5$ are higher in tuff area, MgO and $TiO_2$ are higher in andesite area, $Na_2O_$ is higher in rhyolite area, $SiO_2$, and MnO are higher in arenaceous rock area. Average contents of minor and rare earth elements for geological groups are $Ba\;1278{\sim}1469ppm,\;Be\;1.1{\sim}1.5ppm,\;Cu\;18{\sim}25ppm,\;Nb\;25{\sim}37ppm,\;Ni\;16{\sim}25ppm,\;Pb\;21{\sim}28ppm,\;Sr\;83{\sim}155ppm,\;V\;64{\sim}98ppm,\;Zr\;83{\sim}146ppm,\;Li\;32{\sim}45ppm,\;Co\;7.2{\sim}12.7ppm,\;Cr\;37{\sim}76ppm,\;Cs\;4.8{\sim}9.1ppm,\;Hf\;7.5{\sim}25ppm,\;Rb\;88{\sim}178ppm,\;Sc\;7.7{\sim}12.6ppm,\;Zn\;83{\sim}143ppm,\;Pa\;11.3{\sim}37ppm,\;Ce\;69{\sim}206ppm,\;Eu\;1.1{\sim}1.5ppm,\;Yb\;1.8{\sim}4.4ppm$. According to the comparison of average contents of minor and rare earth elements for geological groups, Pb, Li, Cs, Hf, Rb, Sb, Pa, Ce, Eu, and Yb are higher in granitic gneiss area; Ba, Co, and Cr in schist area; Nb, Ni, and Zr in arenaceous rock area; Sr in tuff area: and Be, Cu, V, Sc, and Zn are such in andesite area.

The Signal Transduciton of Ginsenosides, Active Ingredients of Panax ginseng, in Xenopus oocyte: A Model System for Ginseng Study

  • Nah Seung-Yeol;Lee Sang-Mok
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.66-83
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    • 2002
  • Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

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Diverse Mechanisms of Relaxin's Action in the Regulation of Smooth Muscles and Extracellular Matrix of Vasculature and Fibrosis (혈관과 섬유증의 평활근 및 세포외기질 조절에 대한 릴랙신의 다양한 작용기전)

  • Min, Gyesik
    • Journal of Life Science
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    • v.32 no.2
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    • pp.175-188
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    • 2022
  • Relaxin has been demonstrated to have regulatory functions on both the smooth muscle and extracellular matrix (ECM) of blood vessels and fibrotic organs. The diverse mechanisms by which relaxin acts on small resistance arteries and fibrotic organs, including the bladder, are reviewed here. Relaxin induces vasodilation by inhibiting the contractility of vascular smooth muscles and by increasing the passive compliance of vessel walls through the reduction of ECM components, such as collagen. The primary cellular mechanism whereby relaxin induces arterial vasodilation is mediated by the endothelium-dependent production of nitric oxide (NO) through the activation of RXFP1/PI3K, Akt phosphorylation, and eNOS. In addition, relaxin triggers different alternative pathways to enhance the vasodilation of renal and mesenteric arteries. In small renal arteries, relaxin stimulates the activation of the endothelial MMPs and EtB receptors and the production of VEGF and PlGF to inhibit myogenic contractility and collagen deposition, thereby bringing about vasodilation. Conversely, in small mesenteric arteries, relaxin augments bradykinin (BK)-evoked relaxation in a time-dependent manner. Whereas the rapid enhancement of the BK-mediated relaxation is dependent on IKCa channels and subsequent EDH induction, the sustained relaxation due to BK depends on COX activation and PGI2. The anti-fibrotic effects of relaxin are mediated by inhibiting the invasion of inflammatory immune cells, the endothelial-to-mesenchymal transition (EndMT), and the differentiation and activation of myofibroblasts. Relaxin also activates the NOS/NO/cGMP/PKG-1 pathways in myofibroblasts to suppress the TGF-β1-induced activation of ERK1/2 and Smad2/3 signaling and deposition of ECM collagen.

Geochemical Characteristics of Stream Sediments in the Konyang Area (곤양지역 하상퇴적물에 대한 지구화학적 특성)

  • Park Yaung-Seog;Park Dae-Woo
    • Economic and Environmental Geology
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    • v.39 no.3 s.178
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    • pp.329-342
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    • 2006
  • The purpose of this study is to determine the geochemical characteristics for the stream sediments in the Konyang area. So we can estimate the environment contamination and understand geochemical disaster. We collect the stream sediments samples by wet sieving along the primary channels and slowly dry the collected samples in the laboratory and grind to pass a 200mesh using an alumina mortar and pestle for chemical analysis. Mineralogy, major, trace and rare earth elements are determined by XRD, XRE, ICP-AES and NAA analysis methods. For geochemical characteristics on the geological groups of stream sediments, the studied area was grouped into quartz porphyry area, sedimentary rock area, anorthosite area and gneiss area. Contents of major elements for the stream sediments in the Konyang area were $SiO_2\;41.86{\sim}76.74\;wt.%,\;Al_{2}O_{3}\;9.92{\sim}30.00\;wt.%,\;Fe_{2}O_{3}\;2.74{\sim}12.68\;wt.%,\;CaO\;0.22{\sim}3.31\;wt.%,\;MgO\;0.34{\sim}3.97\;wt.%,\;K_{2}O\;0.75{\sim}0.93\;wt.%,\;Na_{2}O\;0.25{\sim}1.92\;wt.%,\;TiO_{2}\;0.40{\sim}3.00\;wt.%,\;MnO\;0.03{\sim}0.21\;wt.%,\;P_{2}O_{5}\;0.05{\sim}0.38\;wt.%$. The contents of trace and rare earth elements for the stream sediments were $Cu\;7{\sim}102\;ppm,\;Pb\;15{\sim}47\;ppm,\;Sr\;48{\sim}513\;ppm,\;V\;29{\sim}129\;ppm,\;Zr\;31{\sim}217\;ppm,\;Li\;14{\sim}94\;ppm,\;Co\;5.6{\sim}32.1\;ppm,\;Cr\;23{\sim}259\;ppm,\;Cs\;1.7{\sim}8.7\;ppm,\;Hf\;2.1{\sim}109.0\;ppm,\;Rb\;34{\sim}247\;ppm,\;Sc\;4.5{\sim}21.9\;ppm,\;Zn\;24{\sim}609\;ppm,\;Sb\;0.8{\sim}2.6\;ppm,\;Th\;3{\sim}213\;ppm,\;Ce\;22{\sim}1000\;ppm,\;Eu\;0.7{\sim}5.3\;ppm,\;Yb\;0.6{\sim}6.4\;ppm$. Generally, the contents of $Al_{2}O_{3}\;and\;SiO_2$ had a good relationships with each other in rocks but it had a bad relationships in stream sediments for this study area. The contents of $Fe_{2}O_3$, CaO, MnO and $P_{2}O_{5}$ had a good relationships with major and minor elements in stream sediments of this study area. The contents of Co and V in the stream sediments had a good relationships with other toxic elements.

Effects of ${\alpha}_1-Adrenergic$ Stimulation on Contractility and Intracellular $Na^+$ Activity of Guinea Pig Ventricular Muscles (기니픽 심근의 수축력과 세포내 $Na^+$ 활성도에 미치는 ${\alpha}_1-Adrenergic$ 수용체 자극효과)

  • Kim, Jin-Sang;Kang, Hyung-Sub;Chae, Soo-Wan;Lee, Chin-Ok
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.189-199
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    • 1996
  • Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.

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Geochemical Characteristics of Stream Sediments Based on Bed Rocks in the Cheongpung Area (기반암에 따른 청풍지역 하상퇴적물의 지구화학적 특성)

  • Park, Young-Seog;Park, Dae-Woo;Kim, Jong-Kyun;Song, Yeung-Sang;Lee, Jang-Jon
    • Economic and Environmental Geology
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    • v.39 no.6 s.181
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    • pp.675-687
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    • 2006
  • The purpose of this study is to determine the geochemical characteristics of the stream sediments in the Cheongpung area. So that we can understand the natural background and predict the prospects of geochemical disaster, if any. We collected the stream sediments samples by wet sieving along the primary channels and slow dried the collected samples in the laboratory and ground them to pass a 200 mesh using an alumina mortar and pestle for chemical analysis. Miner-alogical characteristics, major, trace and rare earth elements were determined by XRD, XRF, ICP-AES and NAA analysis methods. For geochemical characteristics on the geological group of stream sediments, the studied area was grouped into granitic gneiss area, metatectic gneiss area, Dado tuff area, Yuchi conglomerate area, and Neungju flow area in the Cheongpung area. Contents of major elements for the stream sediments in the Cheongpung area were $SiO_2\;47.31{\sim}72.81\;wt.%,\;A1_2O_3 \;11.26{\sim}21.88\;wt.%,\;Fe_2O_3\;2.83{\sim}8.39\;wt.%,\;CaO\;0.34{\sim}7.54\;wt.%,\;MgO\; 0.55{\sim}3.59\;wt.%,\;K_2O\;1.71{\sim}4.31\;wt.%,\;Na_2O\;0.56{\sim}2.28\;wt.%,\;TiO_2\;0.46{\sim}1.24\;wt.%,\;MnO\;0.04{\sim}0.27\;wt.%,\;P_2O_5\;0.02{\sim}0.45\;wt.%$. The con-tents of trace and rare earth elements for the stream sediments were $Ba\;700ppm{\sim}8990ppm,\;Be\;1.0{\sim}3.50ppm,\;Cu\;6.20{\sim}60ppm,\;Nb\;12{\sim}28ppm,\;Ni\;4.4{\sim}61ppm,\;Pb\;13{\sim}34ppm,\;Sr\;65{\sim}787ppm,\;V\;4{\sim}98ppm,\;Zr\;32{\sim}164ppm,\;Li\;21{\sim}827ppm,\;Co\;3.68{\sim}65ppm,\;Cr\;16.7{\sim}409ppm,\;Cs\;2.72{\sim}37.1ppm,\;Hf\;4.99{\sim}49.2ppm,\;Rb\;71.9{\sim}649ppm,\;Sb\;0.16{\sim}5.03ppm,\;Sc\;4.97{\sim}52ppm,\;Zn\;26.3{\sim}375ppm,\;Ce\;60.6{\sim}373ppm,\;Eu\;0.82{\sim}6ppm,\;Yb\;0.71{\sim}10ppm$.

Geochemistry of Geothermal Waters in Korea: Environmental Isotope and Hydrochemical Characteristics I. Bugok Area (한반도 지열수의 지화학적 연구: 환경동위원소 및 수문화학적 특성 I. 부곡 지역)

  • Yun, Seong-Taek;Koh, Yong-Kwon;Kim, Chun-Soo;So, Chil-Sup
    • Economic and Environmental Geology
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    • v.31 no.3
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    • pp.185-199
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    • 1998
  • Hydrogeochemical and environmental isotope studies were undertaken for various kinds of water samples collected in 1995-1996 from the Bugok geothermal area. Physicochemical data indicate the occurrence of three distinct groups of natural water: Group I ($Na-S0_4$ type water with high temperatures up to $77^{\circ}C$, occurring from the central part of the geothermal area), Group II (warm $Na-HCO_{3}-SO_{4}$ type water, occurring from peripheral sites), Group III ($Ca-HCO_3$ type water, occurring as surface waters and/or shallow cold groundwaters). The Group I waters are further divided into two SUbtypes: Subgroup Ia and Subgroup lb. The general order of increasing degrees of hydrogeochemical evolution (due to the degrees of water-rock interaction) is: Group III$\rightarrow$Group II$\rightarrow$Group I. The Group II and III waters show smaller degrees of interaction with rocks (largely calcite and Na-plagioclase), whereas the Group I waters record the stronger interaction with plagioclase, K-feldspar, mica, chlorite and pyrite. The concentration and sulfur isotope composition of dissolved sulfate appear as a key parameter to understand the origin and evolution of geothermal waters. The sulfate was derived not only from oxidation of sedimentary pyrites in surrounding rocks (especially for the Subgroup Ib waters) but also from magmatic hydrothermal pyrites occurring in restricted fracture channels which extend down to a deep geothermal reservoir (typically for the Subgroup Ia waters). It is shown that the applicability of alkaliion geothermometer calculations for these waters is hampered by several processes (especially the mixing with Mg-rich near-surface waters) that modify the chemical composition. However, the multi-component mineral/water equilibria calculation and available fluid inclusion data indicate that geothermal waters of the Bugok area reach temperatures around $125^{\circ}C$ at deep geothermal reservoir (possibly a cooling pluton). Environmental isotope data (oxygen-18, deuterium and tritium) indicate the origin of all groups of waters from diverse meteoric waters. The Subgroup Ia waters are typically lower in O-H isotope values and tritium content, indicating their derivation from distinct meteoric waters. Combined with tritium isotope data, the Subgroup Ia waters likely represent the older (at least 45 years old) meteoric waters circuated down to the deep geothermal reservoir and record the lesser degrees of mixing with near-surface waters. We propose a model for the genesis and evolution of sulfate-rich geothermal waters.

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Geochemical Study on Geological Groups of Stream Sediments in the Gwangju Area (광주지역 하상퇴적물에 대한 지질집단별 지구화학적 연구)

  • Kim, Jong-Kyun;Park, Yeung-Seog
    • Economic and Environmental Geology
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    • v.38 no.4 s.173
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    • pp.481-492
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    • 2005
  • The purpose of this study is to determine geochemical characteristics for stream sediments in the Gwangju area. We collect the stream sediments samples by wet sieving along the primary channels and dry these samples slowly in the laboratory and grind to under 200mesh using an alumina mortar fur chemical analysis. Major elements, trace and rare earth elements are determined by XRF, ICP-AES and NAA analysis methods. For geochemical characteristics on geological groups of stream sediments, we separate geologic groups which are derived from Precambrian granite gneiss area, Jurassic granite area and Cretaceous Hwasun andesite area. Contents range of major elements for stream sediments in the Gwangju area are $SiO_2\;51.89\~70.63\;wt.\%,\;Al_2O-3\;12.91\~21.95\;wt.\%,\;Fe_2O_3\;3.22\~9.89\;wt.\%,\;K_2O\;1.85\~4.49\;wt.\%,\;MgO\;0.68\~2.90\;wt.\%,\;Na_2O\;0.48\~2.34\;wt.\%,\;CaO\;0.42\~6.72\;wt.\%,\;TiO_2\;0.53\~l.32\;wt.\%,\;P_2O_5\;0.06\~0.51\;wt.\%\;and\;MnO\;0.05\~0.69\;wt.\%.$ According to the AMF diagram for stream sediments and rocks, the stream sediments are plotted on boundary of tholeiitic series and calk alkaline series, which shows that contents of $Fe_2O_3$ are higher in stream sediments than rocks. According to variation diagram of $SiO_2$ versus $(K_2O+Na_2O),$ stream sediments are plotted on subalkaline series. Contents range of trace and rare earth elements for stream sediments in the Gwangiu area are Ba$590\~2170$ppm, Be1\~2.4$ppm, Cu$13\~79$ppm, Nb$20\~34$ppm, Ni$10\~50$ppm, Pb$17\~30$ppm, Sr$70\~1025$ ppm, V$42\~135$ppm, Zr$45\~171$ppm, Li$19\~77$ppm, Co$4.3\~19.3$ppm, Cr$28\~131$ppm, Cs$3.1\~17.6$ppm, Hf$5\~27.6$ppm, Rb$388\~202$ppm, Sb$0.2\~l.2$ ppm, Sc$6.4\~17$ppm, Zn$47\~389$ppm, Pa$8.8\~68.8$ppm, Ce$62\~272$ppm, Eu$1\~2.7$ppm and Yb$0.9\~6$ppm.

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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