| Project/Area Number |
63570037
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General physiology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KITASATO Hiroshi Shiga Univ.Med.Sci., Physiol., Professor, 医学部, 教授 (20079700)
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| Co-Investigator(Kenkyū-buntansha) |
OMATSU-KANBE Mariko Shiga Univ.Med.Sci., Physiol., Assistant, 医学部, 助手 (80161397)
SUGIMOTO Yoshihisa Shiga Univ.Med.Sci., Physiol., Grad.Stud. (30216337)
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| Project Period (FY) |
1988 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1989: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1988: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Pancreatic beta-cell / Dihydropyridine / SITS / Acetazolamide / Na^+ spike / Ca^<2+> spike / 炭酸脱水酵素 / 電気的活動 / アセタゾールアミド / 細胞内pH |
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| Research Abstract |
An increase in the external glucose concentration stimulates both the CO_2-production and the release of insulin from the pancreatic beta-cell. In parallel with an increase in the metabolism of glucose, a depolarization is induced and many spikes are elicited on it. It is well established that the depolarization is associated with a decrease in K^+ conductance. However, the ion species which is carrying the background inward current necessary to a depolarization associated with a decrease in potassium conductance is not identified yet. Experiments conducted in the first year of present research project revealed that acetazolamide (0.lmM), an inhibitor of carbonic anhydrase, lowered the rate of depolarization which was induced by raising the concentration of glucose in bathing solution. During the second year, following findings were obtained:
1. In Ca^<2+>-free Krebs-Ringer solution with 11.1mM glucose Na^+ spikes were observed. The spike in Ca^<2+>-free solution was not suppressed by d
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ihydropyridine (2mg/dl), blocker of Ca^<2+> channel. The Na^+ spike was elicited in the region lower than Ca^<2+> channel was activated. Its duration was 6-8 times longer than that of ordinary Ca^<2+> spikes. An analysis of spike-burst activity in Ca^<2+>-containing solution showed that the Na_+ spike functioned as a booster-potential to generate Ca^<2+> spikes and was responsible for the grouping of Ca^<2+> spikes.
2. Any maneuver to prevent the inflow of Ca^<2+> ions brought about the disappearance of silent phase which separated spike-bursts.
3. SITS (1mM) caused a depolarization in the presence of Ca^<2+>, suggesting that this drug increases the permeability of resting membrane to Ca^<2+>.
4. The addition of SITS to the Ca^<2+>-free solution produced shifts of the undershoot of Na^+ spike and of the threshold potential by -lOmV and -5mV, respectively, showing that an inhibition of HCO_3^-/Cl^- antiport results in cytoplasmic alkalinizalton.
It may be summarized as follows; the continuously produced HCO_3^- ions are always extruded from the cell in exchange for the influx of Cl^- ions, as far as glucose is metabolized, and the passive outflow of the accumulated Cl^- ions carry the main body or the background inward current. Less
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