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Biomedical subjects

Y Oyama

Publications and source records attributed to Y Oyama.

At least 145 records · Page 8Linked to original sources
PubMed1990

Triphenyltin: a potent excitatory neurotoxicant. Its reciprocal effects on voltage-dependent Na and K currents of mammalian brain neuron.

Effects of triphenyltin (TPT) on voltage-dependent sodium current (INa) and two respective potassium currents (delayed and transient potassium currents, IKD and IA) were examined on hippocampal neurons acutely isolated from Wistar rats using a conventional suction pipette technique. TPT at concentrations of 10(-7) to 10(-5) M increased the peak amplitude of INa associated with a prolongation of current decay. On the other hand, TPT started to reduce the peak amplitude of IA at 10(-7) M and completely suppressed it at 10(-5) M or less. The peak amplitude of IKD was also reduced by TPT at 10(-6) M or more. Results suggest that TPT possesses an excitatory neurotoxic action and that TPT as a possible environmental hazard may be harmful for human health.

Animals↗
PubMed1990

GABA affects the glutamate receptor-chloride channel complex in mechanically isolated and internally perfused Aplysia neurons.

The effects of gamma-aminobutyric acid (GABA) on the glutamate receptor chloride ion (Cl-) channel complex were examined in mechanically isolated and internally perfused Aplysia neurons using a concentration clamp technique. GABA at concentrations of 3 x 10(-6) M or more, concentration dependently delayed the recovery of the glutamate response from desensitization. This effect was independent of the GABA response and Cl- redistribution. Muscimol (10(-4) M) mimicked the effect of GABA. However, this was not the case for baclofen (10(-3) M). In some isolated neurons, GABA at concentrations of more than 10(-4) M clearly induced an additional Cl- current, the current kinetics of which were different from those induced by lower concentrations of GABA. Even in the continued presence of 10(-4) M GABA, which desensitized the fast GABA response, higher concentrations of GABA (3 x 10(-4) M to 10(-2) M) elicited the additional current in a concentration-dependent manner. The presence of 10(-4) M glutamate completely abolished this current, indicating cross-desensitization between the glutamate and slow GABA responses. High concentrations of GABA (3 x 10(-2) M) did not activate the glutamate receptor coupled to the large cation channel. The results suggest that, in Aplysia neurons, the glutamate receptor-Cl- channel complex has some similarities to the GABA receptor-Cl- channel complex.

Animals↗
PubMed1990

Inhibition of nicotinic acetylcholine response by atropine in frog isolated sympathetic neurons.

The effect of atropine on nicotinic acetylcholine (ACh) response was studied in frog isolated sympathetic ganglion cells using a 'concentration clamp' technique which combines intra-cellular perfusion with a rapid external solution change within 3 ms. When atropine (more than 6 x 10(-7) M) was simultaneously applied to neurons with ACh (6 x 10(-6) M), the current amplitude was instantaneously reduced in a dose-dependent fashion. Further decreases in the current amplitude were observed in a time-dependent manner during about 20 min after the start of drug-application. Thereafter the current amplitude gradually restored toward the control level in the following 90-120 min in spite of the continuous presence of atropine. However, because d-tubocurarine greatly inhibited the 'restored' current, the last-mentioned is suggested to be also mediated by nicotinic ACh receptor-ionophore complex. Therefore, the inhibitory action of atropine on the peak amplitude of ACh response was examined at 15-20 min after adding the agent. It was dose-dependent but not voltage-dependent. Respective concentrations of atropine and d-tubocurarine causing half the maximum inhibition (IC50) of the peak current evoked by ACh (6 x 10(-6) M) were 1.8 x 10(-5) M and 1.8 x 10(-6) M. Thus, the inhibitory potency was 10 times less than that of d-tubocurarine, an antagonist of nicotinic ACh receptors. The blockade of ACh response by d-tubocurarine was competitive while that by atropine was non-competitive. The current elicited by ACh consisted of two (fast and slow) exponential components plus a steady-state one in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

Influences of trypsin and collagenase on acetylcholine responses of physically isolated single neurons of Aplysia californica.

1. The influences of enzyme treatments (trypsin and collagenase) on responses to perfused acetylcholine were examined on physically isolated single Aplysia neurons, using the voltage-clamp, internal perfusion, and rapid external perfusion technique. 2. During treatment with trypsin (0.025 to 0.1%) for 10 to 30 min at room temperature (22 to 25 degrees C), the peak amplitude of the Na current induced by acetylcholine increased in a time- and dose-dependent manner, and the decay in the continued presence of acetylcholine was slowed. This effect of trypsin treatment was irreversible after washing for 60 min without enzyme. 3. Edrophonium, a cholinesterase inhibitor, has previously been shown to augment the Na acetylcholine response in this preparation by inhibition of acetylcholinesterase. After treatment of the neuron with trypsin, the augmentation after edrophonium was abolished. Furthermore, in the presence of edrophonium, trypsin also failed to increase the response. The dose-response curve for acetylcholine after treatment of trypsin was similar to that in the presence of edrophonium. These results suggest that the modification of the current response by trypsin is a result of removal of cholinesterase activity from the membrane. 4. In contrast to the effects of trypsin, collagenase (0.03 to 0.1%) for 10 to 60 min did not change the current amplitude of the acetylcholine response. However, collagenase treatment did alter the kinetics of the acetylcholine response in a dose-dependent manner, in that the rate of decay was accelerated. A similar acceleration was seen in the acetylcholine responses on other neurons which were due to Cl or K currents, suggesting that the effect was independent on the type of channel. This effect of collagenase was reversible after 30 to 60 min of washing of the neuron. 5. In the presence of edrophonium or after the treatment with trypsin, collagenase still accelerated the current kinetics of the acetylcholine response, indicating that cholinesterase activity is not related to this effect. Furthermore, heated collagenase (presumably inactivated) had a similar action, suggesting that the enzymatic activity of collagenase is not related to the modification of the response. 6. These results suggest that Aplysia acetylcholinesterase is sensitive to trypsin but not to collagenase. However, the preparation of a collagenase used in these studies contains some factor which alters the response to acetylcholine, but this effect is reversible and unrelated to enzymatic activity.

Acetylcholine↗
PubMed1990

[Torsade de Pointes with T wave alternans in a patient receiving moderate dose of chlorpromazine: report of a case].

A case is presented of Torsade de Pointes (TDP) with T wave alternans in a 31-year-old female receiving a moderate dose of chlorpromazine. She was treated in an another hospital for schizophrenia with chlorpromazine (100 mg daily) for several years and admitted to Fujisawa city hospital for numerous episodes of syncope. The electrocardiogram immediately after admission revealed a marked QTc prolongation to 0.81 seconds, T wave alternation without any obvious change in morphology of the QRS complex, and recurrent ventricular tachycardia called TDP. The T wave alternans and TDP were easily abolished by intravenous administration of a bolus of 50 mg lidocaine infusion. The QT interval however, remained prolonged. Physical examination, including cardiac examination, was normal. Serum potassium was 3.6/mEq. Chlorpromazine was discontinued immediately after admission and no further episodes of TDP were seen after the first day. After the QT interval returned to almost normal, chlorpromazine (50 mg daily) was re-administered. Two days after the re-administration, the electrocardiogram revealed marked QT interval prolongation with prominent T waves. Psychotropic drugs, such as chlorpromazine, prolong the QT interval and cause TDP. Chlorpromazine appears to have been responsible for TDP and the T wave alternans in this case. TDP caused by a moderate dose of chlorpromazine has not been previously reported. Lone T wave alternans unaccompanied by changes in the QRS complex is a rare phenomenon and the mechanism underlying T wave alternans remains unknown.

Adult↗
PubMed1990

[Risk factors relating to coronary artery disease in the elderly].

A total of 224 patients with coronary artery disease (CAD) and 167 healthy control beings (C) were evaluated for coronary risk factors. Analysis of low age subset (age less than 55) disclosed hypertension and hypercholesterolemia were more common findings in CAD compared with C. Significantly elevated plasma triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), and reduced high density lipoprotein cholesterol (HDL-C) concentrations were found in CAD, accompanied by significant increase of atherogenic index (AI). In CAD, a decreased number of males and smokers was noted in high age subset (age over 65). Significantly reduced plasma TG and elevated HDL-C were observed in the elderly compared with the young. AI was also significantly higher in this group. Therefore, in CAD, the level of coronary risk factors seemed to be attenuated in the hig age subset compared with the low age group, which was different from the findings in C in whom significantly increased AI was noted in the elderly. In 61 CAD cases, lipid profiles were monitored for 5 years in average. Significant changes recognized during this period were the reduction of TG, LDL-C and AI along with the elevation of HDL-C, suggesting their risk to be improved. To examine the metabolic effects of diuretics, 52 patients with essential hypertension on trichlormethiazide for long periods were subjected to the substitution of this drug by the inhibitor of angiotensin converting enzyme, enalapril, for more than 3 months. At the end of each treatment, measurements of blood sugar (BS) and insulin (IRI) were made together with lipid analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1989

Influences of external Ca2+ on the GABA-induced chloride current and the efficacy of diazepam in internally perfused frog sensory neurons.

The effects of extracellular Ca2+ on the gamma-aminobutyric acid (GABA)-induced Cl- current and the efficacy of diazepam in the facilitation of GABA response were studied in frog isolated sensory neurons, using a 'concentration clamp' technique which combines a suction pipette (internal perfusion and voltage clamp) and a rapid drug application system. When nominal Ca2+-free external solution was changed to the solution containing 2 mM Ca2+, the response elicited by 1 x 10(-5) M GABA was reduced by about 40% of the control obtained in nominal Ca2+-free solution. The dose-response curve for GABA was shifted to the right without affecting the maximum response. It can be suggested that the application of external Ca2+ modulates the affinity of the GABA receptor to its agonist, GABA. Diazepam at the concentration of 3 x 10(-6) M shifted the dose-response curve for GABA to the left without changing the maximum response with or without external Ca2+. However, the augmentatory action of diazepam on the GABA response was reduced in the presence of external Ca2+. Possible mechanisms for inhibitory action of external Ca2+ on the GABA-gated response and the reduced efficacy of diazepam are discussed.

Animals↗
PubMed1989

Alpha-chloralose opens the chloride channel of frog isolated sensory neurons.

The effect of alpha-chloralose on the sensory neurons isolated enzymatically and mechanically from frog dorsal root ganglia was studied using a suction-pipette technique. The threshold concentration of alpha-chloralose was around 3 x 10(-5) M and the current produced by alpha-chloralose saturated at the concentration of 3 x 10(-3) M or more. The dose-response curve for alpha-chloralose provided a Ka value of 6 x 10(-4) M and a Hill coefficient of 1.8. The reversal potential of the response elicited by alpha-chloralose was close to the equilibrium potential for Cl- (ECl), indicating that the current was carried through Cl- channels. The current-voltage relationship indicated that there was little voltage dependence in the alpha-chloralose-induced response. The analysis of the variance of the alpha-chloralose-induced Cl- current fluctuations showed two types of the receptor-ionophore complexes with different channel conductances.

Animals↗
PubMed1989

Effects of chlordiazepoxide, chlorpromazine, diazepam, diphenylhydantoin, flunitrazepam and haloperidol on the voltage-dependent sodium current of isolated mammalian brain neurons.

The effects of chlordiazepoxide, chlorpromazine, diazepam, diphenylhydantoin, flunitrazepam and haloperidol on the voltage-dependent sodium current (INa) were studied on the hippocampal pyramidal neurons, isolated acutely from rats, using a concentration clamp technique. The drugs used here reduced dose-dependently the peak amplitude of INa without affecting its current-voltage relationship. Chlorpromazine was most potent drug inhibiting the INa among them. Chlorpromazine and diphenylhydantoin at the concentration of half inhibition (IC50; 4 x 10(-6) M and 2 x 10(-4) M, respectively) shifted the steady state inactivation curve by more than 20 mV to a hyperpolarizing direction. Both drugs also caused a use-dependent inhibition of the INa. These results suggest that the drugs may block preferentially the inactivated sodium channels. While the concentrations of the drugs for inhibiting the INa are thought to be higher than those for affecting respective receptors for neurotransmitters, the results presented here may provide useful information to elucidate additional modes of action of these drugs in mammalian central nervous system.

Animals↗
PubMed1989

Comparative study on barbiturates using isolated single neurons: GABA-mimetic action and augmentatory action on GABA response.

The comparisons among barbiturate derivatives in both GABA-mimetic action and augmentatory effect on GABA response were made. Experiments were performed on single neurones isolated from frog dorsal root ganglia, using a concentration clamp technique which combines a suction pipette technique (internal perfusion and voltage-clamp) with a rapid external solution exchange within 2 ms. Barbiturates employed here were secobarbital, pentobarbital, hexobarbital and phenobarbital. All barbiturates at the concentrations over 1 x 10(-4) M evoked the chloride current (ICl) dose-dependently. In the GABA-mimetic action of barbiturates the potency was in the order of secobarbital greater than pentobarbital greater than hexobarbital greater than phenobarbital. All barbiturates at the concentrations over 1 x 10(-6) M (but up to 1 x 10(-3) M) augmented the GABA-induced ICl. Potency order of barbiturates in augmenting GABA response was the same as that in their GABA-mimetic actions when the concentration was 1 x 10(-4) M or less. However at the concentration of 1 x 10(-3) M the efficacies of secobarbital and pentobarbital in augmenting GABA response were greatly reduced while the other two barbiturates produced further augmentation.

Animals↗
PubMed1989

Scorpion toxin prolongs an inactivation phase of the voltage-dependent sodium current in rat isolated single hippocampal neurons.

The effects of scorpion toxin on the voltage-dependent sodium current (INa) of CA1 pyramidal neurons isolated from rat hippocampus were studied under the single-electrode voltage-clamp condition using a 'concentration-clamp' technique. The toxin increased the peak amplitude of INa and prolonged its inactivation phase in a time- and dose-dependent manner. Inactivation phase of INa proceeded with two exponential components in the absence (control) and presence of the toxin. In the toxin-treated neurons, both the time constant of slow component and its fractional contribution to the total current increased dose-dependently while the fractional contribution of the fast one decreased in a dose-dependent fashion without changing its time constant. Actions of scorpion toxin on the sodium channels of hippocampal pyramidal neurons were essentially similar to those of peripheral preparations. Therefore, it can be concluded that the sodium channels of mammalian brain neurons have structures and functions similar to peripheral channels.

Animals↗
PubMed1989

Blockade of the voltage-dependent sodium current in isolated rat hippocampal neurons by tetrodotoxin and lidocaine.

The effects of tetrodotoxin and lidocaine on the voltage-dependent sodium current (INa) were studied in the CA1 pyramidal neurons isolated acutely from rat hippocampus using a 'concentration-clamp' technique which combines the intracellular perfusion with a rapid external solution change within a few ms. Tetrodotoxin (TTX) exerted its inhibitory action in time- and dose-dependent manner on the peak amplitude of INa without any apparent effects on both the current activation and inactivation processes of the current. The time course for reaching a steady-state of the inhibitory action shortened with increasing TTX concentration, but the time course of recovery from the inhibition after washing out the toxin was quite the same at any concentrations used. Lidocaine also inhibited dose-dependently the INa, though with slightly accelerating both the activation and inactivation processes. The time courses for reaching the steady-state inhibition and the recovery from the inhibition were much shorter than those in the case of TTX. The results indicate that the voltage-dependent sodium channel of mammalian brain neuron is TTX-sensitive as well as that of peripheral neuron and that the mode of TTX inhibition on the INa is quite different from that of lidocaine.

Animals↗