Biomedical subjects

H Ohmori

Publications and source records attributed to H Ohmori.

At least 55 records · Page 3Linked to original sources

PubMed2000

Epidermal growth factor in urine from patients with bladder cancer.

Epidermal growth factor (EGF), a mitogenic polypeptide with a molecular weight of 6000, is excreted in human urine in nanomolar quantities. Recently, some reports showed that urothelial neoplasm was related to the concentration of EGF in urine. In this study, EGF concentration in urine was measured by enzyme-linked immunosorbent assay (ELISA) in 207 samples from 112 male patients (30-90 years old, median 66.2) who had previously been treated for bladder cancer. Then, we tried to clarify the significance of urinary EGF as a marker for recurrence of bladder cancer in comparison with urine cytology. The samples were collected on occasional follow up cystoscopy. Urine from nine age-adjusted males without urological disease was also measured to obtain normal control values. In 123 samples from patients without tumors, EGF concentrations in urine decreased with age. In 84 samples obtained from patients with recurrent tumor, EGF concentrations were significantly lower than those in 123 samples from patients without tumors (P < 0.001) Furthermore, EGF concentrations in longitudinal samples collected the same patients during tumor recurrence and at the times when no tumor was detected were measured in 56 patients. EGF concentrations in the samples collected during tumor recurrence was significantly lower than that in specimens collected when there was no tumor (P < 0.01). There were no significant differences between the same samples collected during tumor recurrence with regard to tumor grade, stage shape and number of tumors. However, EGF concentration in urine from patients with carcinoma in situ (CIS) was lower than that in specimens from patients without CIS. These results indicate the usefulness of determining the EGF concentration as a marker for detecting bladder cancer recurrence. Urine cytology was also examined in the same series and findings were compared with those of urinary EGF. On cytology, class IV and V were considered positive, and on urinary EGF, less than 10 ng/mgCr were considered positive. Sensitivity was 25% for cytology and 57% for urinary EGF, while specificity was 98% and 66%, respectively. The predictive positive value was 0.88 and 0.53, respectively. With the combined use of urinary EGF and cytology, the sensitivity, specificity and predictive positive value were 68%, 64% and 0.92, respectively. In conclusion, urinary EGF seems to be a useful marker for detecting bladder cancer recurrence if performed in addition to cytology. cancer recurrence if performed in addition to cytology.

Adult↗

PubMed2000

Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography.

The purpose of this study was to examine, by positron emission tomography (PET), the distribution of [18F]fluoro-deoxy-glucose ([18F]FDG) uptake by human muscles during 35 min of running. Thirteen healthy male subjects were studied, seven of whom participated in the exercise study. Running intensity was kept constant such that the subjects' heart rates were maintained at between 140 and 150 beats per minute. [18F]FDG [62.9 (14.8) MBq, mean (SD)] was injected after 15 min of running. PET imaging was started immediately after the running ended. The ratio of [18F]FDG uptake by muscles in runners to that in control subjects (r-c ratio) varied from three to six for the muscles of the foot and leg below the knee joint. The r-c ratio of the medial head of the gastrocnemius (MG) was higher than that of its lateral head (LG). The r-c ratio of the rectus femoris (RF) was lower than that of the other three muscles of the quadriceps femoris (QF). The r-c ratio of inactive muscles located above the waist was approximately 0.7. These results suggest that, during the moderate running of this study: (1) glucose uptake by muscles of the foot and leg below the knee joint clearly increases, (2) the r-c ratio differs significantly among the skeletal muscles, which act synergistically, and (3) glucose uptake by inactive skeletal muscles decreases.

Fluorodeoxyglucose F18↗

PubMed2000

Prevention of collagen-induced arthritis in DBA/1 mice by oral administration of AZ-9, a bacterial polysaccharide from Klebsiella oxytoca.

Collagen-induced arthritis (CIA) is an excellent model of rheumatoid arthritis (RA) in humans that is induced in DBA/1 mice immunized with bovine type II collagen (CII). Here, we report that the induction of CIA was effectively suppressed by oral administration of AZ-9, a purified polysaccharide with the average molecular weight of approximately 200 kDa that was produced by a soil bacterium, Klebsiella oxytoca. When AZ-9 was administered at 125-250 mg/kg/day orally for 9 consecutive days after immunization with CII followed by its administration every 3 days, resulted in a marked reduction of the incidence and the severity of CIA. The serum level of anti-CII IgG2a and the production of IFN-gamma and IL-12 in the draining lymph node (LN) cells were significantly lower in AZ-9-administered mice than the untreated control. These findings suggest that orally administered AZ-9 suppressed CIA through attenuating a Th1-type response to CII. AZ-9 could be fragmented into smaller molecules (3-4 kDa) without losing its suppressive activity.

Administration, Oral↗

PubMed2000

Selective augmenting effects of nitric oxide on antigen-specific IgE response in mice.

Here, we report the enhancing effects of nitric oxide (NO) on an IgE antibody response in mice. Anti-trinitrophenyl (TNP) IgE production induced in vitro in TNP keyhole limpet hemocyanin (KLH)-primed spleen cells was inhibited by approximately 70% when an NO synthase (NOS) inhibitor, L-N(G)-monomethyl-L-arginine, was added at 10(-7)-10(-6) M to the lymphocyte culture. On the other hand, addition of NO-generating agents to the culture resulted in a marked enhancement of the IgE production. In contrast, anti-TNP IgM and IgG1 responses were affected only marginally when the IgE production was either suppressed or augmented by these agents. NO did not directly augment IgE class switching in normal B cells stimulated with lipopolysaccharide and interleukin (IL)-4. NO-mediated augmentation of the IgE response is considered to be of a physiological significance because administration of aminoguanidine (AG), an inhibitor of inducible NOS, to immunized mice resulted in a preferential suppression of anti-TNP IgE production in vivo. This may be explained by the observation that AG-administration increased interferon-gamma expression without changing that of IL-4 in the immunized mice. Taken together, these observations suggest a pathophysiological role of NO in the development of IgE-mediated allergic diseases.

Animals↗

PubMed2000

Identification of additional genes belonging to the LexA regulon in Escherichia coli.

Exposure of Escherichia coli to a variety of DNA-damaging agents results in the induction of the global 'SOS response'. Expression of many of the genes in the SOS regulon are controlled by the LexA protein. LexA acts as a transcriptional repressor of these unlinked genes by binding to specific sequences (LexA boxes) located within the promoter region of each LexA-regulated gene. Alignment of 20 LexA binding sites found in the E. coli chromosome reveals a consensus of 5'-TACTG(TA)5CAGTA-3'. DNA sequences that exhibit a close match to the consensus are said to have a low heterology index and bind LexA tightly, whereas those that are more diverged have a high heterology index and are not expected to bind LexA. By using this heterology index, together with other search criteria, such as the location of the putative LexA box relative to a gene or to promoter elements, we have performed computational searches of the entire E. coli genome to identify novel LexA-regulated genes. These searches identified a total of 69 potential LexA-regulated genes/operons with a heterology index of <15 and included all previously characterized LexA-regulated genes. Probes were made to the remaining genes, and these were screened by Northern analysis for damage-inducible gene expression in a wild-type lexA+ cell, constitutive expression in a lexA(Def) cell and basal expression in a non-inducible lexA(Ind-) cell. These experiments have allowed us to identify seven new LexA-regulated genes, thus bringing the present number of genes in the E. coli LexA regulon to 31. The potential function of each newly identified LexA-regulated gene is discussed.

Amino Acid Sequence↗

PubMed2000

Whole-body energy mapping under physical exercise using positron emission tomography.

We attempted to visualize dynamic adjustment of glucose utilization in humans in the whole-body organs during physical exercise by using three-dimensional positron emission tomography (3D-PET) and [18F]-2-fluoro-deoxy-glucose (FDG). Twelve healthy male volunteers collaborated on the study; six subjects were assigned to the resting control group (C) and the other six to the running group (E). Group E subjects performed running on a flat road for 35 min. After 15 min of running, subjects injected FDG and kept on running thereafter for another 20 min. Group C subjects sat on a comfortable chair in a quiet room for 35 min after the injection of FDG. After scanning by PET, the regions of interest (ROIs) were manually set on brain, heart, thorax, abdomen, lower extremities, and the rest of the body on the corresponding transaxial images. The uptake of FDG in each region was evaluated as the % fraction of FDG accumulation relative to the total amount of whole-body accumulation. The results revealed increase of FDG uptake after running in the lower leg muscles from 24.6 +/- 9.5% to 43.1 +/- 4.7% and in the heart from 2.3 +/- 0.4% to 2.8 +/- 0.6%. The differences were significant (P < 0.05). These increases reflect the rise in energy consumption in leg and heart muscles and were balanced by the reduction of energy consumption in the other part of the body. FDG uptake in the abdominal region reduced from 37.3 +/- 7.2% to 19.7 +/- 4.9%. However, FDG uptake in the brain remained stable, i.e., 11.9 +/- 2.8% at rest and 10.3 +/- 2.5% after exercise. Thus, 3D-PET is a tool to visualize the dynamic adjustment of energy consumption during physical exercise in humans.

Adult↗

PubMed2000

Reactions of grignard reagents with bis- or mono-phosphonium ions in situ generated from Bu3P and dicarboxylic acid dichlorides or omega-ethoxycarbonyl alkanoyl chlorides as a novel method to obtain diketones and ketoesters.

Reactions of Grignard reagents with bis-phosphonium or mono-phosphonium ions in situ generated from BusP and ClCO(CH2)nCOCl (5) or ClCO(CH2)nCO2Et (13) as a tool for preparation of symmetrical diketones or ketoesters were examined. Addition of Bu3P (2.0 eq) to a THF solution of 5 (n=2) at -40 degrees C followed by addition of n-BuMgCl (2.0 eq) gave the corresponding diketone in good yield. When a mixture of BusP and the Grignard reagent (2.0 eq each) was added to the dichloride solution at the same temperature, a better result was obtained. The latter method not with PhMgBr but with n-BuMgCl or MeMgBr was shown to be useful for preparation of symmetrical alkanediones and keto alkanoates from various 5 (n=2-6) and 13 (n=2 or 3), respectively. For synthesis of alpha-diketones or alpha-ketoesters, only PhMgBr entered the reaction, although the yields were not satisfactory. Addition of a mixture of Bu3P (2.0 eq), MeMgBr (1.0 eq) and BuMgCl (1.0 eq) to a THF solution of 5 (n=4) at -40 degrees C afforded a mixture of 2,7-undecanedione and the corresponding two symmetrical diketones, with the yield of the unsymmetrical diketone being 36%.

Chlorides↗

PubMed2000

Resorufin as an electron acceptor in glucose oxidase-catalyzed oxidation of glucose.

Resorufin (1) has been found to act as an electron acceptor in glucose oxidase (GOD)-catalyzed oxidation of glucose. When a 1: 1: 1 mixture of solutions of 1 (5.0 microM), glucose, and GOD (4.0 mg/ml) in phosphate buffer (pH 7.4, 0.1 M) was incubated at 36 degrees C under aerobic conditions and the reaction was followed by a measurement of changes in fluorescence intensity due to 1, only two types of fluorometric traces were observed: (1) when a glucose solution of less than 0.7 mM was subjected to the enzymatic reaction, no consumption of 1 was observed; (2) the reaction with glucose at more than 1.0 mM always consumed 1, affording a regression fluorometric curve, and yet the obtained fluorometric traces could be almost superimposed on one another with no dependence on the glucose concentration. The reasons for the observed phenomena are discussed.

Catalysis↗

PubMed2000

Randomized controlled trial of exercise training for older people (Sendai Silver Center Trial; SSCT): study design and primary outcome.

Physical exercise is expected to improve and maintain physical function in older people, thus promoting health and preventing or postponing the onset of disability in later life. The Sendai Silver Center Trial (SSCT) was a randomized controlled trial designed to evaluate the efficacy of exercise training among healthy free-living older people. Sixty-five eligible participants, aged from 60 to 81 years, were randomly allocated to an exercise group or a control group. The subjects in the exercise group were asked to attend training classes at the Sendai Silver Center, a municipal health and welfare facility in the center of Sendai City, at least twice a week for 25 weeks. Each training class, lasting two hours, started with a warm-up session, followed by an endurance session with a bicycle ergometer, and a resistance exercise training session using rubber films, and ended with a cool-down session. The subjects in the control group were asked to attend recreational classes at the Center twice a month. There were no drop-outs or accidents during the intervention. Comparison of maximum oxygen consumption (VO2max) before and after the 25-week intervention revealed a significant increase in the exercise group (2.1 ml/kg/min) but no significant change in the control group. Our result is equivalent to the participants becoming younger in aerobic capacity by five years after six months of exercise training.

Aged↗

PubMed2000

Modulation of the immune system by the autonomic nervous system and its implication in immunological changes after training.

This review examines the role of the autonomic nervous system in the regulation of the immune system to understand the alteration of immunological parameters under the influence of stressors and exercise. Sympathetic innervation in secondary lymphoid organs plays a major role in immune regulation. Catecholamine released from the nerve terminal serves as the major mediator when bound to adrenergic receptors present on immunocompetent cells. Experiments using chemical and surgical denervation, catecholamine knock-out mice, and receptor antagonist and agonists revealed several important points. Sympathetic nerve activity is generally suppressive for the immunocompetent cells in the blood stream except neutrophils. Sympathetic activity facilitates detachment of T cells and NK cells from blood vessels without affecting functional adhesion molecule expression. Th1 cells express more beta 2 adrenergic receptors than Th2 cells, indicating a greater influence of sympathetic activity on Th1 response. Sympathetic action was also shown to regulate the production of chemokines. Taken together, the sympathetic nervous system does not simply suppress the immune system but might help organize the immune response sequentially and spatially by modulating the distribution of immunocompetent cells.

Animals↗

PubMed1999

Molecular characterization of the hyperpolarization-activated cation channel in rabbit heart sinoatrial node.

We cloned a cDNA (HAC4) that encodes the hyperpolarization-activated cation channel (If or Ih) by screening a rabbit sinoatrial (SA) node cDNA library using a fragment of rat brain If cDNA. HAC4 is composed of 1150 amino acid residues, and its cytoplasmic N- and C-terminal regions are longer than those of HAC1-3. The transmembrane region of HAC4 was most homologous to partially cloned mouse If BCNG-3 (96%), whereas the C-terminal region of HAC4 showed low homology to all HAC family members so far cloned. Northern blotting revealed that HAC4 mRNA was the most highly expressed in the SA node among the rabbit cardiac tissues examined. The electrophysiological properties of HAC4 were examined using the whole cell patch-clamp technique. In COS-7 cells transfected with HAC4 cDNA, hyperpolarizing voltage steps activated slowly developing inward currents. The half-maximal activation was obtained at -87.2 +/- 2.8 mV under control conditions and at -64.4 +/- 2.6 mV in the presence of intracellular 0.3 mM cAMP. The reversal potential was -34.2 +/- 0.9 mV in 140 mM Na+o and 5 mM K+o versus 10 mM Na+i and 145 mM K+i. These results indicate that HAC4 forms If in rabbit heart SA node.

Amino Acid Sequence↗

PubMed1999

Expression of vascular endothelial growth factor in patients with testicular germ cell tumors as an indicator of metastatic disease.

BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) are involved in increased angiogenic activity and disease progression in solid tumors. However, there is no information regarding the association of these angiogenic factors with clinicopathologic findings in testicular germ cell tumors (GCTs). METHODS: The authors examined the expression of VEGF and TP as well as microvessel density in GCTs and their association with clinicopathologic findings. Expression of VEGF and TP and microvessel density were examined immunohistochemically in 80 GCTs, including 33 seminomas (25 tumors with organ-confined disease and 8 with metastasis) and 47 nonseminomatous testicular GCTs (NSGCTs) (20 tumors with organ-confined disease and 27 with metastasis). Expression of VEGF also was examined in four GCTs and one nonneoplastic testis by immunoblotting. RESULTS: VEGF protein was expressed more highly in GCTs compared with nonneoplastic testes. VEGF expression in GCTs was correlated significantly with microvessel count (P < 0.001). Both VEGF expression and microvessel count were correlated with metastasis in seminoma (P = 0.008 and P < 0.001, respectively), but only VEGF expression was identified as statistically significant by multiple regression analysis (P = 0.006). Conversely, four variables (VEGF expression, microvessel count, the presence of venous invasion, and the presence of embryonal carcinoma elements in the primary tumor) were correlated with metastasis in NSGCT (P < 0.001, P < 0.001, P = 0.004, and P = 0.029, respectively). However, multiple regression analysis revealed that only VEGF expression and microvessel count were significant factors for metastasis (P < 0.007 and P < 0.001, respectively). In contrast, high levels of TP were observed in infiltrating cells, but not in the majority of cancer cells. CONCLUSIONS: The findings of the current study suggest that VEGF expression is involved in tumor development, angiogenesis, and metastasis in GCT.

Adolescent↗

PubMed1999

Transcription factor Y-box binding protein 1 binds preferentially to cisplatin-modified DNA and interacts with proliferating cell nuclear antigen.

The Y-box binding protein (YB-1) binds to inverted CCAAT box sequences that are present in the promoter region of many genes. We previously showed that YB-1 is overexpressed in human cancer cell lines that are resistant to cisplatin and that the depletion of YB-1 by transfection of a vector expressing YB-1 antisense RNA increases the sensitivity of human cancer cells to cisplatin. To determine whether YB-1 can bind to cisplatin-modified DNA, we fused YB-1 cDNA to glutathione S-transferase (GST) cDNA and purified the resulting GST fusion protein. When we tested the fusion protein with unmodified or cisplatin-modified oligonucleotides, we found that GST-YB-1 bound more strongly to cisplatin-modified oligonucleotides, as did GST fusion proteins of high mobility group 1 (HMG1), HMG2, and xeroderma pigmentosum group A protein. When we assayed the ability of proliferating cell nuclear antigen (PCNA) to interact with the GST fusion proteins, we observed binding to YB-1 but not to HMG1, HMG2, or xeroderma pigmentosum group A. Subsequent experiments demonstrated that YB-1 and PCNA interact directly via the COOH-terminal region of YB-1. Using immunochemical coprecipitation methods, we observed binding of YB-1 and PCNA in vivo. These results suggest that YB-1 can function as a recognition protein for cisplatin-damaged DNA and that it may be important in DNA repair or in directing the cellular response to DNA damage.

CCAAT-Enhancer-Binding Proteins↗

PubMed1999

IL-4-dependent IgE class switching in an anti-trinitrophenyl B-cell hybridoma after engagement of antigen receptors.

A B-cell hybridoma, TP67.21 that expresses surface anti-trinitrophenyl (TNP) IgM but does not secrete the antibody spontaneously has been reported to differentiate into anti-TNP IgM-secreting cells in response to lipopolysaccharide or engagement of surface IgM. Here, we report isolation and characterization of a subclone, TP67.21E (TP.E) that undergoes isotype switching to IgE in an interleukin (IL)-4-dependent manner. TP.E cells secreted anti-TNP IgE depending on exogenous IL-4 when they were cultured with an anti-IgM antibody for 6-8 days. 8-Mercaptoguanosine, which has been shown to enhance IgE class switching in murine splenic B-cells further augmented the IgE response in TP.E cells. Immunofluorescence microscopy revealed that approximately 1.2% of the cultured cells became positive for intracellular IgE after the stimulation culture. The germline epsilon transcripts were expressed transiently on days 2-4 of the culture, while expression of the productive epsilon transcripts was induced 5 days after the start of the culture, thus suggesting that IgE class switching occurred in TP.E cells under these conditions.

Animals↗

PubMed1999

Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein dinB.

BACKGROUND: The Escherichia coli dinB gene is an SOS gene known to be required for lambda phage untargeted mutagenesis. When over-expressed, it exhibits a potent mutagenic activity without any exogenous treatment to damage DNA. Frameshift mutations at a run of identical bases are most enhanced. The product DinB is structurally related to the E. coli UmuC protein and the Saccharomyces cerevisiae Rev1 and Rad30 proteins, all of which are shown to be involved in bypass synthesis at a DNA lesion. RESULTS: We have cloned and sequenced human and mouse cDNAs encoding a DinB homologue. Their products are highly similar to DinB and less similar to UmuC, Rev1 or Rad30, and hence the genes were named DINB1 for human and Dinb1 for mouse. Both genes were expressed most abundantly in testis. Transient expression of the mouse cDNA in cultured mouse cells resulted in a nearly 10-fold increase in the incidence of point mutations, among which about 30% were frameshift mutations. CONCLUSIONS: The above results suggest that a mutagenic mechanism, a so-called untargeted type, also operates in mammalian cells. Taken together with recent findings that human cells have multiple DNA polymerases for translesion synthesis which are homologous to the S. cerevisiae Rev3 and Rad30 proteins, our results imply that multiple mutagenic pathways are conserved from bacteria to higher eukaryotes.

Amino Acid Sequence↗

PubMed1999

Reactive oxygen species influence the acrosome reaction but not acrosin activity in human spermatozoa.

It is now widely accepted that the higher levels of reactive oxygen species (ROS) produced by damaged or deficient spermatozoa are associated with a loss of motility and a decreased capacity for sperm-oocyte fusion. Furthermore, earlier studies show, under physiological conditions, that some ROS may be involved in capacitation and hyperactivation of human spermatozoa. We measured ROS levels, acrosome reaction (AR) and acrosin activity (AA) in semen samples from suspected subfertile men to reveal the influence of ROS on AR and AA of human spermatozoa. Semen samples were obtained from 60 patients. Samples with > or = 1 x 10(6) leukocytes/mL were excluded from the study. ROS production was determined using a chemiluminescence technique. AR was determined using a triple stain technique. The percentage of acrosome-reacted spermatozoa after low temperature induction of the AR (test value), and the inducibility of AR (= the difference between the test value and the control), were calculated. The AA was analysed by determining the proteolytic potential of spermatozoa on gelatin plates. The mean halo diameter and percentage of halo formation in each sample were measured as AA parameters. Scatter plots of ROS levels and AR parameters showed that the percentage of acrosome reacted spermatozoa and AR inducibility were better in samples with low rather than high ROS levels. On the other hand, there were no apparent similarities between ROS and the AA parameters. Therefore, the percentage of acrosome-reacted spermatozoa and AR inducibility were significantly higher in the low than in the high ROS group (p = 0.028, p = 0.0001, respectively). In addition, there was no significant difference in AA parameters between groups. These findings suggest that lower ROS in semen may have a role in AR but excessive ROS may exert a negative influence on AR, while ROS in semen has no relationship to AA.

Acrosin↗

PubMed1999

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria.

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗

PubMed1999

Li+ and muscarine cooperatively enhance the cationic tail current in rat cortical pyramidal cells.

Li+ is known to facilitate the onset of status epilepticus induced by cholinergic stimulation, although the underlying mechanisms are not clear. Under whole-cell current clamp conditions with a CsCl-based internal solution, cortical pyramidal cells display a single plateau-spike followed by a slow depolarizing afterpotential (DAP) in response to injection of a short current pulse. However, the same current pulse generated a burst of plateau-spikes after application of Li+ (2 mM) and muscarine (10 microM). As similar bursts of plateau-spikes were generated through an enhancement of the slow DAP when [K+]o was raised (Kang et al. 1998), we have investigated the effects of Li+ and muscarine on the Ca2+-dependent cationic current underlying the slow DAP, measured as the slow tail current evoked after the offset of depolarizing voltage pulses. Muscarine enhanced the amplitudes of both early and late components of the slow tail current. This effect of muscarine was markedly potentiated by Li+, while Li+ by itself affected the slow tail current only slightly. Intracellular application of heparin (0.5-1 mg/mL) suppressed the effect of muscarine in the presence of Li+. These results suggest that inositol-trisphosphate-induced Ca2+ release is involved in the cooperative enhancement of the slow tail current, and this cooperation may be one of the mechanisms underlying facilitation of the onset of epilepsy induced by these agents.

Animals↗