Biomedical subjects

H Tatebayashi

Publications and source records attributed to H Tatebayashi.

21 records · Page 2Linked to original sources

PubMed1990

Sodium current kinetics in freshly isolated neostriatal neurones of the adult guinea pig.

Neurones of the neostriatum were freshly dispersed from the adult guinea pig brain. A fast, transient inward Na+ current (INa) was analysed using the whole-cell patch-clamp technique. Upon depolarizations, INa developed with a sigmoidal time course, which was described by m3 kinetics. INa showed an activation threshold of about -60 mV, a peak current at -30 to -20 mV, and a reversal of polarity at +60 mV. The steady-state activation (m infinity) curve for INa had a slope factor of about 9 mV for a change in the rate constant by a factor of e) in the range between -50 mV and -20 mV. Conversely, the backward rate constant (beta m) decreased as the membrane was depolarized (about 31 mV for an e-fold change). The steady-state inactivation (h infinity) curve was well expressed by the Boltzmann's equation with a half-inactivation potential of -62 mV and a slope parameter of 6 mV. The time course of INa decay followed a second-order process, whereas the recovery from inactivation was described as a first-order process. The tau h curve showed a bell-shaped configuration with a maximum value at -60 mV. The forward rate constants (alpha h) decreased as the membrane was depolarized (about 17 mV for an e-fold change) in the range between -50 mV and -20 mV. The backward rate constants (beta h) increased as the membrane was depolarized (about 10 mV for an e-fold change). There was a significant overlap between m infinity and h infinity curves, suggesting a steady influx of Na+ (window current).

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PubMed1989

Modulation of sodium current kinetics by chlorpromazine in freshly-isolated striatal neurones of the adult guinea-pig.

1. The neurones of the striatum were freshly dissociated from the adult guinea-pig brain by enzymatic and mechanical treatments. Sodium channel current kinetics in these neurones were measured using a whole cell variation of the patch-clamp technique. 2. Chlorpromazine, a neuroleptic, in micromolar concentrations reversibly reduced the amplitude of the sodium currents. Activation and inactivation time constants were not affected. The inhibition followed one-to-one binding stoichiometry. 3. The concentration-response curve shifted to the left when the holding potential was less negative. The EC50 shifted from 4.8 microM to 0.9 microM when the holding potential was changed from -120 mV to -70 mV. 4. The steady-state activation curve of the sodium current was not affected by chlorpromazine, whereas the steady-state inactivation curve was shifted in the negative direction. Consequently, the window current which is normally present at a potential range around -50 mV was decreased in the presence of chlorpromazine. 5. Successive sodium currents evoked by a train of depolarizing pulses (30 ms duration) to -10 mV showed a cumulative decrease in size during the application of chlorpromazine. However, such 'use-dependent' block was not observed when the pulse duration was reduced to 1 ms. 6. The recovery from inactivation in the presence of chlorpromazine, was expressed as a second order process. The faster component was similar to the recovery time course of the normal sodium channels. The slower component accounted for the use-dependent effect of chlorpromazine. 7. The results indicate that chlorpromazine binds to the resting sodium channels producing steady-state block at a very negative holding potential. When the membrane is depolarized, chlorpromazine binds to the inactivated form of the sodium channels with much higher affinity and stabilizes them in the inactivated state, slowing their kinetics.

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PubMedDate not supplied

Ion channels as targets for insecticides.

Most insecticides are neurotoxicants causing various forms of hyperexcitation and paralysis in animals. A variety of neuroreceptors and ion channels have been identified as the major target sites of these neurotoxic insecticides. This paper gives the highlights of some of the recent development in this area. Pyrethroids keep the sodium channel open for unusually long times causing a prolonged flow of sodium current. The prolonged sodium current elevates and prolongs the depolarizing after-potential which reaches the threshold membrane potential to initiate repetitive after-discharges. We have developed the method with which the percentage of sodium channel population that needs to be modified to cause repetitive after-discharges can be measured accurately. In rat cerebellar Purkinje neurons, only 0.6% of sodium channels needs to be modified for hyperexcitation resulting in a large toxicity amplification. This concept is applicable to other neuroactive drugs that act through the threshold phenomenon. The mechanisms of selective toxicity of pyrethroids in mammals and insects have been quantitatively determined to be due mainly to the different sensitivity of the sodium channels to pyrethroids and the negative temperature dependence of pyrethroid action on the sodium channels. The degradation of pyrethroids play only a minor role. The negative temperature dependence of pyrethroid action is due to the increased sodium current flow at low temperature. The major site of action of dieldrin and hexachlorocyclohexane is the GABA(A) receptor chloride channel complex. Dieldrin exerts a dual action, initial stimulation and subsequent suppression, and the latter is responsible for hyperexcitation of animals. Dieldrin stimulation requires the gamma2s subunit in the GABA receptor, whereas dieldrin suppression occurs in the presence or absence of the gamma2s subunit.

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