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K Nishikawa

Publications and source records attributed to K Nishikawa.

At least 73 records · Page 4Linked to original sources
PubMed2001

Changing the amino acid specificity of yeast tyrosyl-tRNA synthetase by genetic engineering.

In an attempt to generate mutant aminoacyl-tRNA synthetases capable of charging non-canonical amino acids, a series of yeast tyrosyl-tRNA synthetase (TyrRS) mutants was constructed by site-specific mutagenesis of putative active site residues, which were deduced by analogy with those of Bacillus stearothermophilus TyrRS. Among these mutants, one with the replacement of tyrosine at position 43 by glycine, "Y43G," was found to be able to utilize several 3-substituted tyrosine analogues as substrates for aminoacylation. The catalytic efficiency (k(cat)/K(m)) of mutant Y43G for aminoacylation with L-tyrosine was about 400-fold decreased as compared to that of the wild-type TyrRS. On the other hand, the ability to utilize 3-iodo-L-tyrosine was newly generated in this mutant TyrRS, since the wild-type TyrRS could not accept 3-iodo-L-tyrosine at all under physiological conditions. This mutant TyrRS should serve as a new tool for site-specific incorporation of non-canonical amino acids, such as those in 3-substituted tyrosine analogues, into proteins in an appropriate translation system in vivo or in vitro.

Amino Acid Sequence↗
PubMed2001

Knowledge-based potential defined for a rotamer library to design protein sequences.

A knowledge-based potential for a rotamer library was developed to design protein sequences. Protein side-chain conformations are represented by 56 templates. Each of their fitness to a given structural site-environment is evaluated by a combined function of the three knowledge-based terms, i.e. two-body side-chain packing, one-body hydration and local conformation. The number of matches between the native sequence and the structural site-environment in the database and that of the virtually settled mismatches, counted in advance, were transformed into the energy scores. In the best-14 test (assessment for the reproduction ability of the native rotamer on its structural site within a quarter of 56 fitness rank positions), the structural stability analysis on mutants of human and T4 lysozymes and the inverse-folding search by a structure profile against the sequence database, this function performs better than the function deduced with the conventional normalization and our previously developed function. Targeting various structural motifs, de novo sequence design was conducted with the function. The sequences thus obtained exhibit reasonable molecular masses and hydrophobic/hydrophilic patterns similar to the native sequences of the target and act as if they were the homologs to the target proteins in BLASTP search. This significant improvement is discussed in terms of the reference state for normalization and the crucial role of short-range repulsion to prohibit residue bumps.

Amino Acid Sequence↗
PubMed2001

Agent-selective effects of volatile anesthetics on GABAA receptor-mediated synaptic inhibition in hippocampal interneurons.

BACKGROUND: A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. METHODS: Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. RESULTS: Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. CONCLUSIONS: Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

Anesthetics, Inhalation↗
PubMed2001

Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons.

Inhalational general anesthetics have recently been shown to inhibit neuronal nicotinic acetylcholine (ACh) receptors (nnAChRs) expressed in Xenopus laevis oocytes and in molluscan neurons. However, drug actions on these systems are not necessarily the same as those seen on native mammalian neurons. Thus, we analyzed the detailed mechanisms of action of halothane on nnAChRs using rat cortical neurons in long-term primary culture. Currents induced by applications of ACh via a U-tube system were recorded by the whole-cell, patch-clamp technique. ACh evoked two types of currents, alpha-bungarotoxin-sensitive, fast desensitizing (alpha 7-type) currents and alpha-bungarotoxin-insensitive, slowly desensitizing (alpha 4 beta 2-type) currents. Halothane suppressed alpha 4 beta 2-type currents more than alpha 7-type currents with IC(50) values of 105 and 552 microM, respectively. Halothane shifted the ACh dose-response curve for the alpha 4 beta 2-type currents in the direction of lower ACh concentrations and slowed its apparent rate of desensitization. The rate of recovery after washout from halothane block was much faster than the rate of recovery from ACh desensitization. Thus, the halothane block was not caused by receptor desensitization. Chlorisondamine, an irreversible open channel blocker for nnAChRs, caused a time-dependent block that was attenuated by halothane. These results could be accounted for by kinetic simulation based on a model in which halothane causes flickering block of open channels, as seen in muscle nAChRs. Halothane block of nnAChRs is deemed to play an important role in anesthesia via a direct action on the receptor and an indirect action to suppress transmitter release.

Acetylcholine↗
PubMed2001

Hematopoietic regulatory domain of gata1 gene is positively regulated by GATA1 protein in zebrafish embryos.

Expression of gata1 is regulated through multiple cis-acting GATA motifs. To elucidate regulatory mechanisms of the gata1 gene, we have used zebrafish. To this end, we isolated and analyzed zebrafish gata1 genomic DNA, which resulted in the discovery of a novel intron that was unknown in previous analyses. This intron corresponds to the first intron of other vertebrate Gata1 genes. GFP reporter analyses revealed that this intron and a distal double GATA motif in the regulatory region are important for the regulation of zebrafish gata1 gene expression. To examine whether GATA1 regulates its own gene expression, we microinjected into embryos a GFP reporter gene linked successively to the gata1 gene regulatory region and to GATA1 mRNA. Surprisingly, ectopic expression of the reporter gene was induced at the site of GATA1 overexpression and was dependent on the distal double GATA motif. Functional domain analyses using transgenic fish lines that harbor the gata1-GFP reporter construct revealed that both the N- and C-terminal zinc-finger domains of GATA1, hence intact GATA1 function, are required for the ectopic GFP expression. These results provide the first in vivo evidence that gata1 gene expression undergoes positive autoregulation.

Animals↗
PubMed2001

Isolation, growth, ultrastructure, and metal tolerance of the green alga, Chlamydomonas acidophila (Chlorophyta).

An acidophilic volvocine flagellate, Chlamydomonas acidophila (Volvocales) that was isolated from an acid lake, Katanuma, in Miyagi prefecture, Japan was studied for growth, ultrastructural characterization, and metal tolerance. Chlamydomonas acidophila is obligately photoautotrophic, and did not grow in the cultures containing acetate or citrate even in the light. The optimum pH for growth was 3.5-4.5. To characterize metal tolerance, the toxic effects of Cd, Co, Cu, and Zn on this alga were also studied. Effective metal concentrations, which limited the growth by 50%, EC50 were measured, after 72 h of static exposure. EC50s were 14.4 microM Cd2+, 81.3 microM Co2+, 141 microM Cu2+, and 1.16 mM Zn2+ for 72 h of exposure. Thus, this alga had stronger tolerance to these metals than other species in the genus Chlamydomonas.

Adaptation, Physiological↗
PubMed2001

[Comparative survey of cardiac arrests during anesthesia and surgery in the 1980 s and 1999 s].

A survey of unexpected cardiac arrests, excluding those associated with cardiac surgery, that had occurred during anesthesia and surgery in the period 1980-1999 was conducted. There was no significant difference between the number of such cardiac arrests that occurred in the 1980 s (29/36,159, 0.080%) and the number in the 1990 s (33/37,643, 0.088%). According to the classification by Keenan et al., there were 3 cases (0.0083%) in the 80 s and 4 cases (0.0106%) in the 90 s that occurred due to anesthetic management. Cardiac arrests due to surgery itself significantly decreased from 21 cases in the 80 s to 6 cases in the 90 s, probably due to proper treatment for massive bleeding, a decrease in the number of cases of anaphylactic shock, and the development of novel anesthetics. Conversely, cardiac arrests due to preoperative conditions of the patients significantly increased from 5 cases in the 80 s to 23 cases in the 90 s. This increase seems to be due to an increase in the number of severe and multiple injuries and an increase in complicated major surgery. The increase in number of cases due to preoperative conditions also depends on coronary spasm and cardiac conduction insufficiency. Taking into consideration the improvement in intraoperative monitoring and the development of novel anesthetics in the 90 s, greater efforts should be made by anesthesiologists to reduce the incidence of cardiac arrest due to anesthetic management, and preoperative evaluation of surgical patients needs to be reconsidered.

Anesthesia↗
PubMed2001

[The total-quality-management-analysis of the continuation and discontinuation of alcohol family treatment: a grassroots approach].

A family support/treatment program was provided to thirty-three cases where a drinking family member (identified patient) had shown alcohol related problems but not yet admitted the problem. After a period of between thirteen and twenty-one months of family treatment, fourteen (42.4%) identified patients started their own treatment. The only statistically significant factor that was related to the patients' treatment program participation was the continuation of family members' involvement in a family treatment program. Among the thirty-three cases, a little less than one half (48.5%) continued the family program. In order to increase the patients' participation, it is crucial to encourage family members to continue their family support/treatment program. In order to identify factors that contribute treatment continuation as well as dropouts, workshops were held with those who dropped out and those who continued the family treatment program. The Total-Quality-Management (TQM) affinity and arrow diagram techniques were employed to classify the participants' statements and to find cause-effect relationships among the identified factors, respectively. Five family treatment discontinuation factors were identified: 1) a lack of information about family support program, 2) resistance against a "family change" orientation in family treatment program, 3) family member burnout, 4) a misfit between family needs for immediate problem solutions and what family program offers, and 5) a temporal improvement of patients' drinking problems. While widely varied factors were found to contribute discontinuation, only a very few factors were identified to facilitate the treatment continuation. It was concluded that treatment discontinuation, rather than continuation, was the norm among the families of problem drinkers. Based on the above findings, three kaizen plans were proposed. First, in order to make sure that family members obtain necessary information about the family support/treatment program, a pamphlet would be created and handed out to those who come to family treatment. Second, family support efforts would be emphasized more. Treatment staff is expected to become more cautious with regard to the family behavior change facilitation, especially at the early stage. Third, treatment staff is expected to become more aggressive about contacting family group members when they do not show up to a meeting.

Adult↗
PubMed2001

[The Denial and Awareness Scale (DAS)].

Focusing on denial of drinking problems and raising awareness are two important treatment tasks at the initial stage of alcoholism treatment. However, an objective and clinically practical measure to assess patients' and family members' denial and awareness of alcohol-related problems has not yet been available. The DAS (Denial and Awareness Scale by Aro Ino and Shigeo Tatsuki) was developed in order to predict prognosis and evaluate treatment outcomes of alcoholism patients. The preliminary (DAS-1) patient scale was administered to 370 alcoholism patients. Their family members responded to the DAS-1 family member subscales. The abstinence period was then triangulated among the patient, a family member, and treatment staff members. For the purpose of the current study, 218 responses were used for item analyses and prediction of abstinence periods. Stepwise regression analyses of preliminary (DAS-1) sub-scales demonstrated that several sub-scales significantly predicted abstinence periods. After factor-analytic item re-classification of DAS-I items, DAS-2 was constructed. DAS-2 sub-scales were then regressed onto abstinence periods by a backward stepwise regression method. The analysis using the entire complete sample (N = 189) where both patients and their family members' responses were available demonstrated significantly that "Patient's Awareness" increased abstinence periods while "Family Troubled Feelings" decreased it, and that "Patient's Awareness" also galvanized "Changes in Patient's Mindset". Additional analyses were conducted in order to examine if predictive values of DAS-2 subscales differ according to varying stages of abstinence periods among the study subjects. The results showed that different sets of subscales predicted the abstinence periods depending on the treatment stages, i.e., abstinence within 1 year, 2 years, 3 years, and 4 years. These findings corresponded with the authors' clinical experiences. The current study produced several regression prediction equations utilizing the DAS-2. Further evaluation studies shall examine the effectiveness of the DAS-based prediction/prognosis of the abstinence period of alcoholism patients.

Alcoholism↗
PubMed2001

[Antiangiogenic and antimetastatic effects of toremifene citrate].

In this study, we demonstrated that toremifene citrate (TOR) inhibited the tube formation and migration of human umbilical vein endothelial cells (HUVEC) in vitro. Moreover, TOR suppressed angiogenesis in rabbit cornea and lung metastasis of human fibrosarcoma HT-1080 cells in nude mice. The antiangiogenic activity in vitro was apparent at the concentration of 5 microM which is clinically achievable by oral administration of 120 mg/kg of TOR. These results suggest that clinical treatment with 120 mg/day of TOR might be expected to exhibit antiangiogenesis and antimetastasis effects, in addition to inhibition of estrogen-dependent tumor cell growth.

Angiogenesis Inhibitors↗
PubMed2001

Annual trends and triple therapy--1991-2000.

1. Although the number of cadaver donor transplants did not increase substantially over the past 10 years, unrelated living donor grafts increased from 153 in 1991 to 1,661 through 2000. Use of spousal and other unrelated donor organs contributed to this increase. There was a modest increase in living-related donor transplants from 2,328 in 1991 to 3,451 in 2000. 2. Cadaver donor graft survival at one year improved from 84% in 1991 to 90% in 2000. In contrast, one-year graft survival of living donor transplants only improved from 93% in 1991 to 95% in 2000. 3. Throughout the 10-year period, approximately 13% of transplants were repeat transplants from cadaver donors and roughly 8% were regrafts from live donors. 4. Cadaver donor transplants into White recipients declined from 68% in 1991 to 60% in 2000. For living donors, the percentage of White patients remained constant at about 70%. 5. Graft survival in patients of all races was about equal at one year but diverged at 3 years, with Asians having the highest and Blacks having the lowest 3-year graft survival rates. 6. Average donor age increased from 31.7 in 1991 to 36 in 2000 for cadaveric donor transplants and 37.9 in 1991 to 40.4 in 2000 for living donor transplants. Cadaveric kidneys from donors older than 50 years of age yielded significantly lower 3-year graft survival. 7. Average recipient age for cadaveric donor transplants increased from 42.1 in 1991 to 46.8 in 2000. The average recipient age for living donor transplants also increased steadily from 33.7 in 1991 to 42.9 in 2000. There was relatively little effect on graft survival rates for advanced age recipients. 8. The percentage of sensitized recipients receiving cadaver donor grafts declined from 27% in 1991 to 21% in 2000. Similarly, sensitized recipients receiving living donor grafts decreased from 17% in 1991 to 13% in 2000. Graft survival in patients with more than 50% PRA was lower at 3 years for patients receiving cadaveric donor grafts. Highly sensitized patients receiving living donor grafts had graft survival rates similar to those who were not sensitized. 9. Cold ischemia times decreased from an average of 24.2 hours in 1991 to 18.9 hours in 2000. Improved graft survival rates over those 10 years were noted in all groups, and even cold ischemia times more than 36 hours yielded 3-year graft survivals comparable to those with lower cold ischemia times in 1998. 10. The need for dialysis has remained constant at about 23% over the last 10 years for patients receiving kidneys from cadaveric donors. The rate of dialysis for patients receiving kidneys from living donors was about 5% for each of the 10 years examined. First day anuria increased from 11% in 1991 to 16% in 2000 for cadaver donor transplants and 3% in 1999 to 5% in 2000 for living donor grafts. 11. Cadaveric donor patients requiring dialysis had a 3-year graft survival rate of 63% if there was no first day anuria and 56% if they had first day anuria. This is in contrast to 80% 3-year graft survival for those with immediate diuresis and no need for dialysis. The 3-year graft survival rate for those receiving living donor grafts and needing dialysis was 58% if they had first day diuresis and 41% if they ware anuric on the first day. Conversely, those who had first day function and did not require dialysis had 89% 3-year graft survival. 12. Among the patients receiving cadaveric grafts with first day diuresis there was a marked reduction in those with rejection, from 21% in 1991 to 5% in 2000. Similarly, for this type of patient receiving living donor grafts, the reduction was 17% in 1991 to 5% in 2000. However, graft survival among these patients did not change significantly. The greatest improvement was noted in those with first day anuria and no rejection. 13. Patients who did not require dialysis, and had rejection prior to discharge decreased markedly from 17% in 1991 to 3% in 2000 in those receiving cadaveric grafts and 15% in 1991 to 3.9% in 2000 for those receiving living donors. Graft survival of cadaveric transplants in those needing dialysis, with and without rejection, improved the most in the 10 year period. 14. Hospitalization days for cadaveric transplant recipients were reduced from 19 days in 1991 to 10 days in 2000 and 16 days in 1991 to 8 days in 2000 for recipients of living donor grafts. There was an increase in discharge serum creatinine values from 2.3 mg/dl in 1991 to 3.3 mg/dl in 2000 for cadaver donor grafts. 15. Double therapy was utilized for about 15% of cadaveric and living donors. There was a sharp increase in induction therapy, peaking at 51% in 1994 and decreasing to 5% by 2000 for cadaveric donor transplants. Induction did not improve graft survival for either cadaver or living donor transplant recipients. 16. Triple therapy improved graft survival of White and Black patients, but did not affect the half-lives in either race. 17. The lower graft survival from older donors was not affected by triple therapy for cadaver donor transplants. Triple therapy removed the donor age effect for recipients of living donor grafts. 18. Triple therapy practically eliminated the effect of sensitization for cadaveric donor grafts. Both double and triple therapy virtually eliminated the sensitization effect for living donors. 19. Triple therapy significantly improved the survival of kidneys with more than 36 hours cold ischemia time so that 3-year graft survival was 76% at 3 years compared with 81% for kidneys stored 1-12 hours. 20. Triple therapy improved the 3-year graft survival of kidneys with first day anuria from 50% for double therapy to 69% for triple therapy in cadaver donor transplants. For living donor transplants, there was a similar improvement from 57% with double therapy to 72% with triple therapy. 21. Triple therapy improved the 3-year cadaveric graft survival rate of kidneys requiring dialysis from 51% with double therapy to 67% for triple therapy. There was a similar improvement for living donors needing dialysis from 37% to 61% at 3 years.

Adolescent↗
PubMed2000

Structural/functional assignment of unknown bacteriophage T4 proteins by iterative database searches.

Among the total of 274 orfs within bacteriophage T4, only half have been reasonably well characterized, and the functions of the rest have remained obscure. In order to predict the molecular functions of the orfs, a position-specific iterated (PSI)-BLAST search of bacteriophage T4 against the sequence database of known 3D structures was carried out. PSI-BLAST is one of the most powerful iterative sequence search methods using multiple sequence alignment, with the ability to detect many more proteins with distant homology than standard pairwise methods. The 3D structures of proteins are considered to be better preserved than the sequences, and the detected distantly homologous proteins are likely to possess highly similar 3D structures. Thirteen orfs of phage T4, whose homologues were not detected by standard pairwise methods, were found to have significantly homologous counterparts by this method. The plausibility of the results was confirmed by checking whether important residues at substrate/ligand-binding sites were conserved. Among them, two orfs, vs.1 and e.1, which are similar to Escherichia coli lytic enzyme and MutT protein, respectively, had not been studied previously. Also, gp rIIA, a rapid lysis protein, whose gene structure had been intensively studied during the development of molecular biology in the 1950s and yet whose molecular function remains unknown, has an N-terminal domain that is significantly similar to the N-terminal region of the heat shock protein Hsp90.

Amino Acid Sequence↗
PubMed2000

Protein structure comparison using the markov transition model of evolution.

A number of automatic protein structure comparison methods have been proposed; however, their similarity score functions are often decided by the researchers' intuition and trial-and-error, and not by theoretical background. We propose a novel theory to evaluate protein structure similarity, which is based on the Markov transition model of evolution. Our similarity score between structures i and j is defined as log P(j --> i)/P(i), where P(j --> i) is the probability that structure j changes to structure i during the evolutionary process, and P(i) is the probability that structure i appears by chance. This is a reasonable definition of structure similarity, especially for finding evolutionarily related (homologous) similarity. The probability P(j --> i) is estimated by the Markov transition model, which is similar to the Dayhoff's substitution model between amino acids. To estimate the parameters of the model, homologous protein structure pairs are collected using sequence similarity, and the numbers of structure transitions within the pairs are counted. Next these numbers are transformed to a transition probability matrix of the Markov transition. Transition probabilities for longer time are obtained by multiplying the probability matrix by itself several times. In this study, we generated three types of structure similarity scores: an environment score, a residue-residue distance score, and a secondary structure elements (SSE) score. Using these scores, we developed the structure comparison program, Matras (MArkovian TRAnsition of protein Structure). It employs a hierarchical alignment algorithm, in which a rough alignment is first obtained by SSEs, and then is improved with more detailed functions. We attempted an all-versus-all comparison of the SCOP database, and evaluated its ability to recognize a superfamily relationship, which was manually assigned to be homologous in the SCOP database. A comparison with the FSSP database shows that our program can recognize more homologous similarity than FSSP. We also discuss the reliability of our method, by studying the disagreement between structural classifications by Matras and SCOP.

Databases, Factual↗
PubMed2000

Differential regulation of human RecQ family helicases in cell transformation and cell cycle.

Three human RecQ DNA helicases, WRN, BLM and RTS, are involved in the genetic disorders associated with genomic instability and a high incidence of cancer. RecQL1 and RecQL5 also belong to the human RecQ helicase family, but their correlation with genetic disorders, if any, is unknown. We report here that in human B cells transformed by Epstein-Barr virus (EBV), human fibroblasts and umbilical endothelial cells transformed by simian virus 40, the expression of WRN, BLM, RTS and RecQL1 was sharply up-regulated. In B cells this expression was stimulated within 5-40 h by the tumor promoting agent phorbol myristic acetate (PMA). Interestingly, RecQL5beta, an alternative splicing product of RecQL5 with a nuclear localization signal, is expressed in resting B cells without significant modulation of its synthesis by EBV or PMA, suggesting it has a role in resting cells. We also roughly determined the number of copies per cell for the five RecQ helicase in B cells. In addition, levels of the different RecQ helicases are modulated in different ways during the cell cycle of actively proliferating fibroblasts and umbilical endothelial cells. Our results support the view that the levels of WRN, BLM, RTS and RecQL1 are differentially up-regulated to guarantee genomic stability in cells that are transformed or actively proliferating.

Adenosine Triphosphatases↗
PubMed2000

Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons and inhibitory interneurons.

A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal neurons in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role during anesthesia. The aim of this study was to investigate effects of a general anesthetic, halothane, on membrane and synaptic properties of rat hippocampal interneurons. GABA receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in visually identified CA1 pyramidal cells and interneurons located at the border of stratum lacunosum-moleculare and stratum radiatum. Halothane (0.35 mm congruent with 1.2 vol%) depressed evoked IPSC amplitudes recorded from both pyramidal cells and inhibitory interneurons. Also, halothane considerably prolonged the decay time constant of evoked IPSCs in pyramidal cells and interneurons. The frequencies of miniature IPSCs were increased by halothane (two- to threefold) in both types of neuron. On the other hand, halothane effects on resting membrane potentials were variable but minimal in both types of neurons. In current-clamp recordings, halothane depressed EPSP amplitudes and increased IPSP amplitudes recorded from both types of neurons. In addition, halothane increased the failure rate of synaptically evoked action potentials. Taken together, these data provide evidence that halothane increases GABA(A) receptor-mediated synaptic inhibition between synaptically connected interneurons and depresses excitatory transmission, similar to effects observed in pyramidal neurons.

Action Potentials↗