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M Iino

Publications and source records attributed to M Iino.

At least 19 recordsLinked to original sources
PubMed1992

Calcium-dependent immediate feedback control of inositol 1,4,5-triphosphate-induced Ca2+ release.

The temporal and spatial distribution of increases in intracellular Ca2+ concentration is an important factor in cellular signal transduction. Inositol 1,4,5-trisphosphate (InsP3) plays a key part in agonist-induced Ca2+ release, which can take place abruptly and in a confined space by a mechanism that is not fully understood. Here we analyse the kinetics of InsP3-induced Ca2+ release following flash photolysis of caged InsP3 or caged Ca2+, and demonstrate that Ca(2+)-dependent immediate feedback control is an important determinant of the time course of Ca2+ release. The positive feedback mechanism is also important for the 'loading dependence' of InsP3-induced Ca2+ release. Furthermore, our results support the operation of positive cooperativity in channel opening and feedback control augments the steep InsP3 concentration-Ca2+ release relation. These inherent properties of InsP3-induced Ca2+ release are expected to give rise to temporally abrupt and/or spatially confined Ca2+ release within the cell.

Animals↗
PubMed1992

Enhancement of Ca2+-induced Ca2+ release in calpain treated rabbit skinned muscle fibers.

Calpain treatment of rabbit skinned muscle fibers resulted in proteolysis of junctional foot protein or Ca2+ release channel of the sarcoplasmic reticulum. Electrophoretic and immunoblot analyses indicate that calpain cleaves off approximately 130 kDa peptide from the N-terminus. After such treatment, Ca2+ capacity of the sarcoplasmic reticulum remained normal and both Ca2+ and adenine nucleotide dependence of Ca2+-induced Ca2+ release mechanism were retained. However, the Ca2+-activated Ca2+ release rate was increased by two fold after the proteolysis. The results suggest the presence of functional domains in the junctional foot protein, and the N-terminus domain controls the activity of the Ca2+ channel without changing Ca2+ and nucleotide sensitivities.

Animals↗
PubMed1992

Presence of functionally different compartments of the Ca2+ store in single intestinal smooth muscle cells.

Studies in smooth muscle bundles have shown the presence of functionally different compartments of Ca2+ store, one (S alpha) sensitive to both caffeine and inositol 1,4,5-trisphosphate (IP3), and the other (S beta) sensitive only to IP3. Ca2+ release in isolated single smooth muscle cells from guinea pig taenia caeci was studied to see if both compartments exist within a cell. Responses to caffeine and carbachol were consistently observed but were abolished after treatment with ryanodine, while intracellular application of IP3 induced Ca2+ release after the treatment, albeit smaller in size than control. Thus S alpha and S beta coexist in a single smooth muscle cell and agonist-induced Ca2+ release requires whole store to be loaded with Ca2+.

Animals↗
PubMed1992

[Effects of halothane, caffeine and ryanodine on the intracellular calcium store in blood mononuclear cells].

To evaluate the possibility of using blood cells in the screening test for susceptibility to malignant hyperthermia (MH), we examined the effect of halothane and caffeine on cytoplasmic free calcium concentration ([Ca]i) in mononuclear cells. Blood mononuclear cells were isolated from guinea pigs or normal human volunteers, loaded with fura-2 AM and changes in the calcium signal (340nm/380nm ratio) after the application of halothane and/or caffeine were measured. Halothane above 5 mM caused a large increase in [Ca]i, but this increase was mostly abolished by the removal of extra-cellular calcium using EGTA. On the other hand, caffeine caused no observable change in the calcium signal. Pre-treatment with ryanodine did not change the calcium signal brought about by halothane or ionomycin. We conclude from this study that there is no calcium-induced calcium release (CICR) mechanism detectable by this method in blood mononuclear cells. As we consider that the main cause of the typical MH is the abnormality in the CICR mechanism, it seems difficult to screen MH susceptibility by using blood mononuclear cells. Further studies will be necessary using MH susceptible swines or patients.

Animals↗
PubMed1991

Excitatory synapse in the rat hippocampus in tissue culture and effects of aniracetam.

Excitatory synaptic connections between rat hippocampal neurons were established in tissue culture. The electrophysiological and pharmacological properties of these synapses were studied with the use of the tight-seal whole-cell recording technique. The excitatory postsynaptic current (EPSC) in a dissociated CA1 neuron evoked by stimulation of an explant from the CA3/CA4 region of the hippocampus had two distinct components in Mg(2+)-free medium. The fast component was abolished by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (2 microM), whereas the slow component was abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) (50 microM). In solution containing 1 mM Mg2+, the peak amplitude of the fast component was almost linearly related to the membrane potential. In contrast, the conductance change underlying the slow component of the EPSC was voltage-dependent with a region of negative-slope conductance in the range of -80 to -20 mV. A nootropic drug, aniracetam, increased both the amplitude and duration of the fast component of the EPSC in a concentration-dependent manner in the range of 0.1-5 mM, whereas it had no potentiating effect on the slow component. Aniracetam (0.1-5 mM) similarly increased current responses of the postsynaptic neuron to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). Current responses to quisqualate and glutamate in the presence of D-APV were also potentiated by aniracetam. However, neither NMDA- nor kainate-induced current was potentiated by 1 mM aniracetam.

2-Amino-5-phosphonovalerate↗
PubMed1991

Effects of adenine nucleotides on inositol 1,4,5-trisphosphate-induced calcium release in vascular smooth muscle cells.

Effects of adenine nucleotides on the inositol 1,4,5-trisphosphate (IP3)-induced Ca release (IICR) mechanism were studied in smooth muscle cells of the guinea pig portal vein. A microfluorometry method of fura-2 was used to measure Ca release from saponin-skinned thin muscle strips (width approximately 200 microns, thickness 50-70 microns, length 2-3 mm). About 80% of ionomycin-releasable Ca store was sensitive to IP3, of which approximately 20% was also sensitive to caffeine. The rate of Ca release by 0.1 microM IP3 depended biphasically on ATP concentration in the absence of Mg2+; it was dose-dependently enhanced by ATP up to approximately 0.5 mM, and above this concentration the enhancement became smaller. However, the decline of enhancement of the IICR at the higher ATP concentrations was absent at IP3 concentrations greater than 1 microM. This suggests competitive antagonism between IP3 and ATP. Clear effects of ATP were observed not only at pCa 7 or 8, where the Ca-induced Ca release was not activated, but after a ryanodine treatment to excise the functional compartment that possessed the Ca-induced Ca release mechanism. ATP had no effect on the rate of Ca leakage in the absence of IP3 even at pCa 5.5 after the ryanodine treatment. Therefore, ATP has direct biphasic effects on the IP3-induced Ca release mechanism. The Ca release induced by 0.1 microM IP3 at pCa 7 was potentiated not only by ATP, but by 0.5 mM ADP, AMP, or beta, gamma-methyleneadenosine 5'-triphosphate. 0.5 mM GTP had only a little effect on the IP3-induced Ca release. These results extend the functional similarities between Ca- and IP3-induced Ca release mechanisms in that adenine nucleotides enhance Ca release. Millimolar concentration of ATP, which is present physiologically, will shift the dose-response relation of IP3 toward the higher IP3 concentration and enhance the maximal effect of IP3. Thus, ATP is expected to assist the Ca release by higher concentrations of IP3 while having less effect on the Ca release by low levels of IP3. These effects of ATP may be important in the switching of Ca release from the intracellular Ca store by IP3.

Adenine Nucleotides↗
PubMed1991

Two types of kainate response in cultured rat hippocampal neurons.

1. Two different types of kainate response were recorded in cultured rat hippocampal neurons with the use of the whole-cell and outside-out configurations of the patch-clamp technique. 2. There was an outward rectification in the current-voltage (I-V) plot of the kainate-induced current (type I response) in relatively large neurons bearing a morphological resemblance to young pyramidal cells. In smaller neurons with elliptical somata and fine neurites, the kainate response was characterized by a remarkable inward rectification in the I-V plot of the kainate-induced current and a significant permeability to Ca2+ (type II response). 3. Both type I and type II responses were negligible below 2 microM and almost saturated at 500 microM kainate. The concentrations producing half-maximal responses and the Hill coefficients were 68 microM and 1.76 and 56 microM and 1.21 for type I and type II responses, respectively. Both responses were suppressed similarly by the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 4. The mean single-channel conductance (gamma) of the type II kainate response was estimated, from the relation between the whole-cell mean currents and current variances, to be 8.7 pS. The power spectrum for the current noise was fitted with the sum of two Lorentzians with cutoff frequencies (fc) of 61.1 +/- 1.4 and 327.8 +/- 10.5 Hz (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1990

Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci.

Ca2+ dependence of the inositol 1,4,5-trisphosphate (IP3)-induced Ca release was studied in saponin-skinned smooth muscle fiber bundles of the guinea pig taenia caeci at 20-22 degrees C. Ca release from the skinned fiber bundles was monitored by microfluorometry of fura-2. Fiber bundles were first treated with 30 microM ryanodine for 120 s in the presence of 45 mM caffeine to lock open the Ca-induced Ca release channels which are present in approximately 40% of the Ca store of the smooth muscle cells of the taenia. The Ca store with the Ca-induced Ca release mechanism was functionally removed by this treatment, but the rest of the store, which was devoid of the ryanodine-sensitive Ca release mechanism, remained intact. The Ca2+ dependence of the IP3-induced Ca release mechanism was, therefore, studied independently of the Ca-induced Ca release. The rate of IP3-induced Ca release was enhanced by Ca2+ between 0 and 300 nM, but further increase in the Ca2+ concentration also exerted an inhibitory effect. Thus, the rate of IP3-induced Ca release was about the same in the absence of Ca2+ and at 3 microM Ca2+, and was about six times faster at 300 nM Ca2+. Hydrolysis of IP3 within the skinned fiber bundles was not responsible for these effects, because essentially the same effects were observed with or without Mg2+, an absolute requirement of the IP3 phosphatase activity. Ca2+, therefore, is likely to affect the gating mechanism and/or affinity for the ligand of the IP3-induced Ca release mechanism. The biphasic effect of Ca2+ on the IP3-induced Ca release is expected to form a positive feedback loop in the IP3-induced Ca mobilization below 300 nM Ca2+, and a negative feedback loop above 300 nM Ca2+.

Animals↗
PubMed1990

Permeation of calcium through excitatory amino acid receptor channels in cultured rat hippocampal neurones.

1. N-methyl-D-aspartate (NMDA)-, quisqualate- and kainate-induced currents were recorded in cultured rat hippocampal neurones using the whole-cell voltage-clamp technique. To isolate the inward currents carried by Ca2+ and other divalent cations (Sr2+, Ba2+, Mn2+ and Mg2+), both Na+ and K+ in the control external solution were replaced with the impermeant cation N-methylglucamine (NMG). 2. Replacement of Na+, K+ and Ca2+ with NMG abolished NMDA-, quisqualate- and kinate-induced inward currents. In Na(+)-, K(+)-free (abbreviated simply as Na(+)-free) solution containing 10 mM-Ca2+ NMDA caused prominent inward currents at -60 mV. In this solution with the internal solution containing 165 mM-Cs+, the reversal potential of the NMDA-induced current was -5.0 +/- 0.7 mV (n = 36), indicating a value of PCa/PCs = 6.2 for the ratio of the permeability coefficients of Ca2+ and Cs+ according to the constant-field equation. 3. NMDA elicited inward current responses at -60 mV in Na(+)-, Ca2(+)-free solution containing 10 mM-Sr2+, Ba2+, or Mn2+, but not in Na(+)-free, 10 mM-Mg2+ solution. On the basis of reversal potential measurements, the permeability sequence of NMDA receptor channels among the divalent cations was determined to be Ba2+ (1.2) greater than Ca2+ (1.0) greater than Sr2+ (0.8) greater than Mn2+ (0.3) much greater than Mg2+ (less than 0.02). 4. The reversal potential of the quisqualate-induced current was more negative than -80 mV in Na(+)-free, 10 mM-Ca2+ solution, indicating a value of PCa/PCs less than 0.18. 5. Kainate-induced current responses were classified into two types. In the type I response the reversal potential of the kainate-induced current was more negative than -80 mV in Na(+)-free, 10 mM-Ca2+ solution, indicating that the Ca2+ permeability of this type of kainate channel is as low as that of the quisqualate channel. In the neurones which showed a type I response, there was a tendency of outward rectification in the current-voltage plots of the kainate response in control solution. 6. In the type II response kainate caused prominent inward currents at -60 mV in Na(+)-free, 10 mM-Ca2+ solution. The reversal potential was -23.3 +/- 5.6 mV (n = 17), indicating a permeability ratio PCa/PCs = 2.3. In the neurones which showed a type II response, a remarkable inward rectification was observed in the current-voltage plots of the kainate response in control solution. 7. Type II kainate channels showed relatively poor selectivity among divalent cations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Suppression by extracellular K+ of N-methyl-D-aspartate responses in cultured rat hippocampal neurons.

1. The effects of increasing K+ concentration in Mg2(+)-free extracellular solution on N-methyl-D-aspartate (NMDA)-induced current were studied in cultured rat hippocampal neurons with the use of the whole-cell and outside-out configurations of the patch-clamp technique. 2. When the K+ concentration in the external solution was increased by replacement of Na+ with isomolar K+, the amplitude of the NMDA-induced current decreased in a concentration-dependent manner. The effect of K+ was almost saturated at 100 mM, when the NMDA response was reduced to 12% of that in K(+)-free, 150 mM Na+ solution. Increasing the external K+ concentration did not affect either the kainate- or quisqualate-induced current in these experimental conditions. 3. Increase in the external K+ concentration reduced the NMDA-induced current almost equally over the whole range of membrane potential tested (-60-30 mV). The reversal potential of the NMDA-induced current was not significantly shifted by the replacement of Na+ with K+. 4. A rise in the external K+ concentration to 100 mM did not reduce the single-channel conductance of the NMDA channel, whereas it reduced the mean open time to about two-thirds of that in the control external solution. 5. The suppressed activation of the NMDA receptor channel in high-K+ environments may have a functional significance to alleviate entry of toxic Ca2+ into neurons of the CNS in pathological conditions such as hypoxia and ischemia.

Animals↗
PubMed1990

Calcium release mechanisms in smooth muscle.

Properties of the intracellular Ca store were studied using saponin-skinned fiber bundles of guinea pig smooth muscles using a fluorescent Ca indicator method. There exist two Ca release mechanisms in the Ca store: Ca-induced Ca release (CICR) and inositol 1,4,5-trisphosphate (IP3)-induced Ca release (IICR) mechanisms. The smooth muscle Ca store consists of two compartments: one (S alpha) has both CICR and IICR, and the other (S beta) has only IICR. The smooth muscle CICR is activated by greater than 1 microM Ca2+, has essentially the same properties with that in striated muscles, and is open-locked by ryanodine. After ryanodine treatment, therefore, the Ca uptake capacity of S alpha is selectively lost ('functional removal') with no effect on S beta. The IICR is Ca2(+)-dependent: Ca2+ enhances the IICR below 300 nM, but has also an inhibitory effect above this concentration. Therefore, Ca2+ acts on the IICR in a positive feedback manner when muscle tension is about to rise, making IP3 more effective, but this feedback is cut off as the tension approaches the maximum. ATP enhances the IICR as is the case in the CICR. 'Functional removal' of S alpha in intact bundles by ryanodine was used to estimate the role of Ca release in agonist-induced contractions. Ca release from the S alpha is important at least in the initial phase of contractions; and in the pulmonary artery, most of the activator Ca2+ originates from S alpha.

Animals↗
PubMed1990

[Clinical study on abnormalities of lower esophageal sphincter (LES) function in infancy and childhood with special reference to gastroesophageal reflux].

For the purpose of clarifying lower esophageal sphincter function, which is representative of antireflux competence, 51 normal newborn and early infants and 28 newborn and infants with gastroesophageal reflux were examined by standardized manometric studies. Barium studies and 24-hour pH monitoring in the distal esophagus were also performed, and the following results were obtained. 1) In normal infants, there was no correlation between LES pressure and age, but LES length increased with age. 2) LES Pressure of GER infants (22.2 +/- 6.4 cmH2O) was lower than normal infants (37.6 +/- 8.8 cmH2O). This indicated LES function was lower in GER infants. 3) In GER infants, LES pressure increased to within normal range with clinical improvement. The critical point of LES pressure was 27 cmH2O. 4) In radiological studies in GER infants there was no correlation between the grade of Barium regurgitation and LES pressure, or between HIS angle, Fornix Index and LES pressure. 5) On 24-hour pH monitoring, pH score of GER infants was very much higher than that of normal infants. LES incompetence din GER infants was also recognized in this investigation. Esophageal manometric study was very useful for diagnosis of LES dysfunction and assessment of therapeutic effect. For evaluation of anti-reflux cardiac function, multiple approaches were valuable, including not only manometric studies but also radiologic studies and 24-hour pH monitoring.

Age Factors↗
PubMed1990

Further investigations of red cell deformability with nickel mesh.

Although the filtration method has been widely employed in red cell deformability studies, the structural irregularity of the pores of a Nuclepore polycarbonate membrane has always been a major problem. Anegawa, T. et al. (Clin. Hemorheol., 7, 1987) obtained a higher reproducibility with the filtration method using a newly designed thin metal film with pores engraved by the photofabrication technique. We further studied the pressure - flow rate relationship of red cell suspension employing this nickel mesh. The filtration of red cell suspensions through the nickel mesh was not influenced by leukocytes contamination or added leukocytes up to a leukocyte count of 250 cells/mm3 within an experimental limitation. On the other hand, the flow was greatly influenced by leukocytes contamination when the polycarbonate membrane was used. The nickel mesh was found to be useful in detecting major determinants of red cell deformability, such as cell geometry and internal cellular viscosity, and in detecting abnormalities of red cell deformability in a patient with microangiopathic hemolytic anemia. In conclusion, the present study clearly shows that the nickel mesh is preferable for investigating red cell deformability to the polycarbonate membrane from a quantitative point of view. This material should contribute to the physiologic and clinical investigation of red cell deformability.

Anemia, Hemolytic↗
PubMed1990

[Huge splenic metastasis from hepatocellular carcinoma; a case report].

A 62-year-old man was admitted to the hospital because of a left upper quadrant mass. He had undergone treatment for hepatocellular carcinoma for 1 year and 7 months. Dynamic CT and angiography revealed a huge hypovascular mass in the spleen. An autopsy confirmed a splenic metastasis of hepatocellular carcinoma with a massive hemorrhage.

Carcinoma, Hepatocellular↗