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N Akaike

Publications and source records attributed to N Akaike.

At least 235 records · Page 13Linked to original sources
PubMed1991

Delayed potassium current and non-specific outward current in pyramidal neurones acutely dissociated from rat hippocampus.

The electrical property of delayed K+ currents (IKD) was studied in pyramidal neurones freshly isolated from the rat hippocampal CA1 region. The IKD was separated pharmacologically from other membrane currents. Activation and inactivation processes of the IKD were highly voltage-dependent in the potential range between -30 and +20 mV. The steady-state inactivation of IKD was observed at -100 mV or more positive potentials. The potential for half steady-state inactivation was -65 mV. The IKD was fully inactivated around -20 mV. Reactivation of IKD consisted of two exponential components. After pharmacological suppression of IKD, the small amount of residual voltage-dependent outward current (one-fifteenth to one-twentieth of IKD amplitude) was observed. The current kinetics was similar to that of IKD and greatly reduced by substitution of internal K+ with N-methyl-D-glucamine+. It was concluded that the properties of IKD was basically similar to those of IKD in other excitable tissues and that the residual current might be non-specific outward current.

4-Aminopyridine↗
PubMed1991

Interaction of various non-steroidal anti-inflammatories and quinolone antimicrobials on GABA response in rat dissociated hippocampal pyramidal neurons.

Interaction of various non-steroidal anti-inflammatory drugs (NSAIDs) and quinolone antimicrobials with gamma-aminobutyric acid (GABA)A receptor-Cl- channel complex was investigated in rat dissociated hippocampal CA1 neurons by using whole-cell mode patch-clamp technique. Neither NSAIDs nor quinolones alone affected the GABA-induced chloride current (ICl). In the presence of norfloxacin (NFLX), one of quinolones, some NSAIDs suppressed the GABA response in a concentration-dependent manner. The inhibitory potency of NSAIDs was 4-biphenylacetic acid (BPA), a metabolite of fenbufen much greater than indomethacin = naproxen greater than mefenamic acid greater than diclofenac greater than piroxicam. The results suggest that fenbufen, indomethacin and naproxen in the presence of quinolones may induce the epileptogenic neurotoxicities via pharmacological interaction with GABAA receptor.

4-Quinolones↗
PubMed1991

Quinolones do not interact with NMDA receptor in dissociated rat hippocampal neurons.

Interaction of quinolone antimicrobials and fenbufen, anti-inflammatory agents, with the N-methyl-D-aspartate (NMDA) receptor was investigated in rat hippocampal neurons with the conventional patch-clamp technique. Simultaneous applications of quinolones and a metabolite of fenbufen had no effects on the glutamate- and NMDA-induced currents. The blocking effects of Mg2+ and MK-801 on NMDA responses were also unaffected. Therefore, the convulsive action induced by quinolones and fenbufen does not seem to involve the function change of NMDA receptor.

4-Quinolones↗
PubMed1991

Rapid interaction of tetraethylammonium with delayed K+ channel in mammalian brain neuron.

In order to study the rapidity of interaction between tetraethylammonium (TEA) and the delayed K+ channel of the mammalian brain neuron, TEA was applied to isolated rat hippocampal pyramidal neurons in a time-controlled sequence with a voltage step using a concentration clamp technique. TEA at a concentration of 30 mM, externally applied, started to decrease the delayed K+ current (IKD) without any detectable delay after the onset of the drug application. The inhibitory action of TEA reached a steady state within 10 ms while the full recovery from the inhibition required 20-30 ms after removing TEA from the external solution. Ba2+ at a concentration of 30 mM also reduced the IKD without any detectable delay. However, it took 40-60 s to reach the steady state of inhibition. Full recovery from the inhibition by Ba2+ was obtained around 60 s after removal of Ba2+ from the external solution. It is suggested that the interaction of TEA with the delayed K+ channel is much faster than that of Ba2+.

Animals↗
PubMed1991

Differential blockade of bicuculline and strychnine on GABA- and glycine-induced responses in dissociated rat hippocampal pyramidal cells.

The inhibitory effects of bicuculline (BIC) and strychnine (STR) on GABA- and glycine-induced responses were studied in the rat dissociated hippocampal CA1 pyramidal neurons in whole-cell mode by using the conventional patch-clamp technique. Both GABA and glycine elicited inward Cl- currents in a dose-dependent manner and had almost the same maximal responses. The half-maximum dose (Ka) and Hill coefficient were 6.4 microM and 1.1 for the GABA response, and 74 microM and 1.5 for the glycine response. BIC and STR antagonized both GABA and glycine responses in a competitive manner. The blocking potency of BIC and STR on the GABA response was comparable. The half inhibition dose (IC50) was 2.7 microM for BIC and 6.7 microM for STR. STR blocked the glycine response about 3,000 x more effectively than BIC. The IC50 was 28 nM for STR and 100 microM for BIC. The BIC and STR did not have voltage-dependent blocking effects on either GABA or glycine responses. Neither GABA nor glycine showed outward rectification in their current-voltage relationships. The functional role of glycine in the rat hippocampal CA1 region is discussed.

Animals↗
PubMed1991

Acetylcholine receptors in dissociated nucleus basalis of Meynert neurons of the rat.

Electrical and pharmacological properties of acetylcholine (ACh)-induced currents in neurons dissociated from the nucleus basalis of Meynert (nBM) of immature (2-week-old) rats were investigated with the whole-cell mode of the patch-clamp technique. At a holding potential (VH) of -50 mV, ACh (10(-4)M) evoked a transient inward current mimicked by nicotine (InACh), followed by a sustained outward current mimicked by carbamylcholine (ImACh). The KD values were 1.2 x 10(-4) M for ImACh and 8.7 x 10(-7) M for ImACh. The reversal potential of ImACh was close to EK. The ImACh was determined to be elicited via the M2 muscarinic receptor, based on the differences in sensitivity to muscarinic antagonists such as pirenzepine and AF-DX-116.

Acetylcholine↗
PubMed1991

Modulatory action of cholinergic drugs on N-methyl-D-aspartate response in dissociated rat nucleus basalis of Meynert neurons.

The effect of cholinergic drugs on N-methyl-D-aspartate (NMDA)-activated responses in neurons dissociated freshly from the nucleus basalis of Meynert (nBM) of immature and mature rats were investigated with the whole-cell patch-clamp technique. The NMDA (10(-4) M)-evoked inward current (INMDA) consisted of transient peak and successive steady-state components. In mature neurons, the peak component was suppressed by pretreatment with acetylcholine (ACh, 10(-12)-10(-5) M) but facilitated by higher concentrations (greater than 10(-5) M). Regardless of the concentration, ACh had no effect on INMDA of immature neurons. The results suggest that ACh behaves as either inhibitory or excitatory modulator of glutaminergic transmission in nBM neurons of adult mammals depending on ACh concentration.

Acetylcholine↗
PubMed1991

Acetylcholine-activated ionic currents in isolated paratracheal ganglion cells of the rat.

The electrophysiological property of acetylcholine (ACh)-induced current (IACh) was studied in paratracheal ganglion cells freshly isolated from rat trachea under whole-cell voltage-clamp condition. IACh consisted of an initial transient peak component and a successive steady-state plateau one. The peak component increased in a sigmoidal fashion with increasing ACh concentration. The IACh was mimicked by nicotine. The current-voltage relationship for the IACh showed inward rectification at the positive membrane potentials beyond the reversal potential (EACh). In a K(+)-free solution, the EACh was close to the Na+ equilibrium potential. The IACh was blocked by either D-tubocurarine or atropine. The ion selectivity of ACh-activated channels to various monovalent cations was weak, and similar to those of other preparations. It was concluded that the IACh in rat paratracheal ganglion cells was mediated by nicotinic receptor activation.

Acetylcholine↗
PubMed1991

Calcium channel in isolated outer hair cells of guinea pig cochlea.

The physiological and pharmacological properties of the Ca2+ channel in outer hair cells (OHCs) freshly isolated from guinea pig cochlea were investigated using a whole-cell patch-clamp technique. The Ca2+ current (ICa) was activated from a membrane potential of -20 mV and reached peak value around +20 mV in external solution containing 20 mM Ca2+ at a holding potential of -70 mV. The peak amplitude of ICa increased in a hyperbolic manner with increasing extracellular Ca2+ concentration. The ion selectively was Ba2+ much greater than Ca2+ greater than or equal to Sr2+. It was concluded that the Ca2+ channel in OHCs of guinea pig is of the L-type.

Action Potentials↗
PubMed1991

The possible involvement of tetrodotoxin-sensitive ion channels in ischemic neuronal damage in the rat hippocampus.

To determine the role of tetrodotoxin-sensitive ion channels in post-ischemic selective neuronal death, the effect of tetrodotoxin on ischemia-induced brain cell injury was studied in rats. The animals were subjected to 20 min of cerebral ischemia in a four vessels occlusion model. Thirty min before ischemia, tetrodotoxin at a dose of 10(-7) or 10(-6) M was topically applied into the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those of a vehicle-injected group. The average cell density of CA1 pyramidal neurons ipsilateral to the injection (cells/mm, mean +/- S.E.M.) was 27 +/- 7 (n = 6) in the vehicle-treated group, and 56 +/- 13 (n = 6) and 83 +/- 17 (n = 6) in the group treated with tetrodotoxin at doses of 10(-7) and 10(-6) M, respectively. Tetrodotoxin mitigated the ischemic hippocampal neuronal damage in a limited but dose-dependent manner. This suggests that activation of tetrodotoxin-sensitive ion channels might contribute to the process of the ischemic neuronal damage.

Animals↗
PubMed1991

Effects of nerve growth factor and cAMP on expression of acetylcholine receptor in PC12 cells.

The developmental change in acetylcholine-induced current (IACh) was investigated in PC12 cells cultured in the presence or absence of either nerve growth factor (NGF) or 8-Br-cAMP for 10 days. Currents were recorded in the whole-cell mode of the conventional patch-clamp technique. Morphological observations revealed that control cells do not undergo a change in morphology during culture. NGF-treated cells developed long neurites and had dense connections with other cells. 8-Br-cAMP-treated cells developed short neurites, and did not have dense connections. Control cells did not show a change in the mean density of IACh (VH = -80 mV) during the culture period. NGF-treated cells had a maximal increase in the current density of IACh at 5 days after the beginning of treatment, and did not show any further increase until 10 days. 8-Br-cAMP-treated cells had a decrease in current density during the first 6 days, but recovered to the control level after 7 days of treatment. It is concluded that maximal expression of ACh receptors occurs in the relatively early days of development, and that intracellular cAMP does not contribute greatly to their expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Strychnine-induced potassium current in isolated dorsal root ganglion cells of the rat.

1. Effects of strychnine (Str) on the dissociated dorsal root ganglion (DRG) cells of the rat have been investigated in whole-cells configuration by a conventional patch-clamp technique. 2. gamma-Aminobutyric acid (GABA)-induced Cl- current (ICl) increased sigmoidally with increasing concentration. The half-maximal response (Ka) was 3 x 10(-5) M and the Hill coefficient was 1.5. Both Str and bicuculline inhibited the GABA-induced ICl in a concentration-dependent manner. 3. Str itself could elicit the current at concentrations over 10(-5) M, at which concentrations the GABA response was completely suppressed. The concentration-response curve for the Str-induced current was bell-shaped, and a nearly maximum response occurred at 3 x 10(-4) M. A transient 'hump' current appeared immediately after the wash-out of external solution containing high concentrations of Str over 3 x 10(-4) M. 4. The Str-induced outward current and a transient 'hump' current were augmented by the removal of extracellular K+ and were suppressed by the substitution of intracellular K+ for Cs+. But the current was not sensitive to extracellular Na+, Ca2+ and Cl-. 5. The reversal potential of Str-induced current (EStr) was -75 mV, which was close to the K+ equilibrium potential (EK = -76.3 mV). The change of EStr for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. The reversal potential of the 'hump' current was also close to EK. 6. The Str-induced outward current was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. 7. The Str-induced K+ current was not affected by internal perfusion of bis(gamma-aminophenoxy)ethane-N, N,N',N-tetraacetic acid (BAPTA), indicating that the Str response does not result in the activation of K+ conductance by the intracellular Ca2+.

Animals↗
PubMed1991

Mechanisms of the anticholinergic effect of SUN 1165 in comparison with flecainide, disopyramide and quinidine in single atrial myocytes isolated from guinea-pig.

1. The mechanism of the anticholinergic effect of SUN 1165 on the acetylcholine (ACh)-induced K+ current (IK.ACh) was examined and compared with those of flecainide, disopyramide and quinidine in single atrial myocytes, in a whole-cell configuration by use of the concentration-jump technique. This technique combines an intracellular perfusion and a rapid exchange of external solution surrounding the voltage-clamped single myocyte within 2 ms. 2. In the cells loaded with guanosine-5'-triphosphate (GTP), 100 microM, the muscarinic ACh response, (IK.ACh), was mediated by GTP-binding proteins. The concentrations of the test drugs that produced a half-maximal inhibition of ACh (1 microM)-induced IK.ACh (IC50) were 29 microM for SUN 1165, 3.6 microM for flecainide, 1.7 microM for disopyramide, and 1.6 microM for quinidine. The blockade of IK.ACh by SUN 1165 and its recovery from the inhibition occurred within a few seconds. Disopyramide had a similar rapid action, while the effects of flecainide and quinidine occurred much more slowly within a few tens of seconds. 3. In cells loaded with 100 microM guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S, a nonhydrolysable GTP analogue), the K+ channel was uncoupled from the muscarinic receptors and activated irreversibly due to direct activation of GTP-binding proteins by GTP gamma S. SUN 1165 and disopyramide had a weak inhibitory effect (IC50 greater than 100 microM for both), while flecainide and quinidine depressed the GTP gamma S-induced K+ current with similar potencies to the cases of ACh-induced currents; IC50 was 5.3 microM for flecainide and 4.4 microM for quinidine. 4 These results suggest that the mechanisms underlying the anticholinergic effects of these antiarrhythmic drugs are different; disopyramide and high concentrations of SUN 1165 mainly block muscarinic ACh receptors in atrial myocytes, while flecainide and quinidine inhibit the K+ channel itself and/or GTP-binding proteins.

Acetylcholine↗
PubMed1991

Kinetic properties of the caffeine-induced transient outward current in bull-frog sympathetic neurones.

1. The kinetic properties of the caffeine-induced transient outward current (ICaff) of the bull-frog sympathetic neurone were investigated using the extremely rapid concentration-jump technique. By setting the holding potential at the equilibrium potential for Cl- (-50 mV), the involvement of the Ca(2+)-activated Cl- current was suppressed. Using a Na(+)-free (Tris) external solution, the involvement of the Na(+)-dependent sustained outward current was eliminated. The 'M' conductance was also occluded by pre-treatment with muscarine. Under these experimental conditions, ICaff consisted of a TEA-sensitive Ca(2+)-activated K+ current. 2. When the latent period from the application of caffeine until the onset of ICaff (termed the ICaff latency) was measured, 10 mM-caffeine gave a latency of 10.5 +/- 0.7 ms (n = 14, mean +/- S.E.M.) at 22 degrees C. The latency was independent of caffeine concentration between 3 and 30 mM. 3. The ICaff latency was temperature-dependent; it was shortened when the temperature was elevated. 4. Both the time to peak and half-decay time of ICaff were decreased with increasing caffeine concentration. In each cell, these parameters decreased by increasing the amplitude of ICaff. 5. At 22 degrees C, the time to peak and the half-decay time of ICaff elicited by 10 mM-caffeine showed a linear relationship, and this relationship was preserved on either elevating or lowering the temperature. On lowering the temperature (12 degrees C), the time to peak shortened whereas the half-decay time was prolonged. On elevating the temperature (32 degrees C), the time to peak was prolonged whereas the half-decay time was shortened. 6. When EGTA in the intracellular solution was replaced by equimolar BAPTA, the time to peak was prolonged while the half-decay time was shortened. 7. It is concluded that caffeine can activate ICaff, with a time course in the order of milliseconds, and that the kinetics of activation and inactivation of ICaff reflect the time-dependent change in the total amount of intracellular free Ca2+.

Acetylcholine↗
PubMed1991

Dual effect of glycine on isolated rat suprachiasmatic neurons.

Pharmacological properties of strychnine-sensitive and -insensitive glycine receptors have been investigated in rat suprachiasmatic nucleus (SCN) neurons. Because the SCN neurons were too small for stable intracellular recordings by the glass-microelectrode technique, a conventional whole cell mode patch-clamp technique was employed on the acutely dissociated SCN neurons. Dissociated SCN neurons were morphologically heterogeneous and could be distinguished into several types. All cells responded to glycine in a concentration-dependent manner. The glycine-induced current was primarily Cl- sensitive and competitively blocked by strychnine. The SCN neurons also responded to excitatory amino acids: glutamate, quisqualate, kainate, and N-methyl-D-aspartate (NMDA). Responses to glutamate and aspartate, which are endogenous neurotransmitter candidates, were enhanced by adding glycine. Glycine especially augmented the maximum response to NMDA in a full concentration range. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) did not suppress the strychnine-sensitive glycine response but did suppress the strychnine-insensitive NMDA response in a competitive manner for glycine. The results suggest that glycine influences neural activity in the SCN as a classical inhibitory neurotransmitter and an excitatory neuromodulator.

Animals↗
PubMed1991

gamma-Aminobutyric acid-induced response in acutely isolated nucleus solitarii neurons of the rat.

The gamma-aminobutyric acid (GABA)-induced macroscopic Cl- current (ICl) was investigated in acutely isolated nucleus tractus solitarii (NTS) neurons by a conventional patch-clamp technique combined with a rapid drug application method. The GABA- and muscimol-induced ICl increased in a concentration-dependent manner. The reversal potentials were close to the Cl- equilibrium potential. Pentobarbital sodium (PB) itself elicited a current. Bicuculline (BIC), strychnine (STR), picrotoxin, benzylpenicillin (PCG), Cd2+, and Zn2+ suppressed the GABA response in a concentration-dependent manner. Both BIC and STR shifted the concentration-response curve for GABA response to the right, whereas PCG suppressed the maximum response without affecting the threshold, indicating that BIC and STR antagonized competitively and PCG noncompetitively. The inhibitory action of PCG on GABA response was in a highly voltage-dependent manner. PB shifted the concentration-response curve for GABA response to the left. The augmentatory effect of PB was voltage dependent.

Animals↗
PubMed1991

Kinetic properties of T-type Ca2+ currents in isolated rat hippocampal CA1 pyramidal neurons.

1. T-type Ca2+ channels producing a transient inward current were studied in pyramidal neurons acutely isolated from the ventral portion of rat hippocampal CA1 region. Membrane currents were recorded by the suction-pipette technique, which allows for internal perfusion under a single-electrode voltage clamp. 2. In all cells superfused with external solution containing 10 mM Ca2+, the T-type Ca2+ current was evoked by step depolarization to potentials more positive than -60 mV from a holding potential of -100 mV and reached a peak in the current-voltage relationship around -30 mV at 20-22 degrees C. 3. Activation and inactivation processes of T-type Ca2+ current were highly potential dependent, and the latter was fitted by a single exponential function. 4. Steady-state inactivation of T-type Ca2+ current could be fitted by a Boltzmann's equation with a slope factor of 6.0 and a half-inactivated voltage of -79 mV. 5. Recovery from inactivation of T-type Ca2+ current was not a single exponent. The major component of recovery (60-90% of total) was voltage sensitive with a time constant of 215 ms at -100 mV. 6. Amplitude of the T-type Ca2+ current depended on the external Ca2+ concentration. The ratio of peak amplitude in the individual current-voltage relationships of Ca2+, Ba2+, and Sr2+ currents passing through T-type Ca2+ channel was 1.0:0.85:1.32. The current kinetics were much the same. 7. All kinetic properties, including activation and inactivation, as well as the amplitude of T-type Ca2+ current, were temperature sensitive with Q10 (temperature coefficient) values of 1.7-2.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗