Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Phencyclidine

Addictive drugs, such as opioids, ethanol, cocaine, amphetamine, and phencyclidine (PCP), affect many functions of the nervous system and peripheral organs, resulting in severe health problems. G protein-activated inwardly rectifying K+ (GIRK, Kir3) channels play an important role in regulating neuronal excitability through activation of various Gi/o protein-coupled receptors including opioid and CB1 cannabinoid receptors. Furthermore, the channels are directly activated by ethanol and inhibited by cocaine at toxic levels, but not affected by methylphenidate, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) at toxic levels. The primary pharmacological action of PCP is blockade of N-methyl-D-aspartate (NMDA) receptor channels that are associated with its psychotomimetic effects. PCP also interacts with several receptors and channels at relatively high concentrations. However, the molecular mechanisms underlying the various effects of PCP remain to be clarified. Here, we investigated the effects of PCP on GIRK channels using the Xenopus oocyte expression system. PCP weakly but significantly inhibited GIRK channels at micromolar concentrations, but not Kir1.1 and Kir2.1 channels. The PCP concentrations effective in inhibiting GIRK channels overlap clinically relevant brain concentrations in severe intoxication. The results suggest that partial inhibition of GIRK channels by PCP may contribute to some of the toxic effects after overdose

マムシグサ(サトイモ科)における雌雄性のサイズ依存性と花粉流動に関する研究

取得学位：博士(理学)，学位授与番号：博甲第714号，学位授与年月日：平成17年3月22

被子植物の葉緑体DNAのPCR-SSCP解析に適したプライマーセット

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Modeling Transceiver BER-OSNR Characteristic for QoT Estimation in Short-Reach Systems

A transceiver BER-OSNR model is validated and applied the Q-factor estimation for short-reach systems. Experiments using pluggable transceivers with commercial DSPs show that the modeling and estimation errors are less than 0.05 dB and 0.15 dB, respectively

Free Perforation in Crohn\u27s Disease

Rare complication of free perforation in Crohn\u27s disease was clinically reviewed on the basis of surgical experiences with Crohn\u27s diseases. 1) Free perforation occurred in younger patients with steroid therapy. 2) There are no close correlation with the time duration of the disease affection. 3) The fortuitous locations of free perforation were the ileum and the ascending colon with multiple perforations. 4) One expired with postoperative sepsis on 55 days after surgery because of delay in diagnosis and treatment, although the other one was very well one year and one month following surgery. It was emphaseized that physicians should be aware of rare complication of free perforation in the follow-up of younger patients with Crohn\u27 disease in the use of steroid

Accuracy of Nonlinear Interference Estimation on Launch Power Optimization in Short-Reach Systems with Field Trial

We show that even the approximate formula of the Gaussian noise model is accurate enough for launch power optimization in short-reach systems. We compare simulation and field trial results using two fiber types, showing the estimation error of signal Q-factor is less than 0.02 dB

Evidence for a Common Founder and Clinical Characteristics of Japanese Families with the MAPT R406W Mutation

Background/Aim: Mutations in MAPT cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Patients with the MAPT R406W mutation were reported to show phenotypic heterogeneity in different ethnic backgrounds. We here report the clinical and genetic characteristics of Japanese families with the R406W mutation. Methods: We examined the clinical and neuroimaging features of 6 patients from three families with the R406W mutation. We determined the genotypes of intragenic MAPT single-nucleotide polymorphisms (SNPs) and the flanking microsatellite markers to search for a common founder. Results: The initial symptom was memory loss with the average age at onset being 54 years. Anterograde amnesia with episodic memory impairment was the predominant phenotype. Behavioral and personality changes or parkinsonism is not a prominent feature. A brain MRI study revealed marked atrophy of the medial temporal lobe. Genetic analysis of SNPs and microsatellite markers revealed that the affected members of the three families share common genotypes. Conclusion: The findings of the affected members in this study, which corroborate previously reported findings of European families, suggest that the R406W mutation may represent a phenotype of predominant anterograde amnesia in FTLD-17. Our genetic data suggest that a founder effect may account for some families with the R406W mutation

Targeted expression of stepfunction opsins in transgenic rats for optogenetic studies

Abstract Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light. In bigenic pups carrying the Phox2B-Cre driver, ChRFR(C167A) was specifically expressed in the rostral parafacial respiratory group (pFRG) in the medulla, where endogenous Phox2b immunoreactivity was detected. These neurons were sensitive to blue light with an increase in the firing frequency. Thus, this transgenic rat actuator/reporter system should facilitate optogenetic studies involving the effective in vivo manipulation of the activities of specific cell fractions using light of minimal intensity