| Project/Area Number |
05808076
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | KAGOSHIMA UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
SORIMACHI Masaru Kagoshima University School of Medicine, Department of Physiology, Professor, 医学部, 教授 (70036440)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGAMI K Kagoshima University School of Medicine, Department of Physiology, assistant, 医学部, 助手 (30041354)
AKAIKE N Kyusyu University School of Medicine, Depertment of Physiology, Professor, 医学部, 教授 (30040182)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Ciliary ganglion cells / Nicotine / Muscarine / Calcium / Sodium / Fura-2 / SBFI / Ca ; Icium channel antagonists / 毛様体神経節 / Calciun / sodium / patch clamp / 細胞内Ca^<2+> / ニコチン様受容体 / ムスカリン様受容体 / 電位依存性Caチャンネル |
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| Research Abstract |
Chick embryo ciliary ganglion neurons were acutely isolated, and the mechanisms underlying the increases in the cytosolic Ca^<2+> concentration ([Ca]_<in>) induced by nicotine and muscarine were examined using fura-2 microfluorometry and whole cell clamp technique. Both the nicotine- and muscarine-induced [Ca]_<in> increases were inhibited by both L- and N-type Ca^<2+> channel blockers and potentiated by an L-type Ca^<2+> channel agonist, Bay-K-8644. Nicotine, but not muscarine, increased the cytosolic Na^+ concentration ([Na]_<in>) as measured by SBFI microfluorometry, and this [Na]_<in> increase was inhibited by nicotinic receptor channel antagonists. These results suggest that nicotine increased Na^+ influx through nicotinic receptor channels resulting in membrane depolarization, which in turn increased Ca^<2+> influx through Ca^<2+> channels. However, nicotine still increased inflexes of Ca^<2+> and Mn^<2+> in the absence of external Na^+, suggesting that nicotinic receptor channels are permeable not only to monovalent cations but also to Ca^<2+> and Mn^<2+>. Muscarine caused a slow inward current, which became smaller at a hyperpolarized potential but not reversed, suggesting that the current was elicited by the inhibition of M-current. In fact, the muscarine-induced increase in [Ca]_<in> persisted after treatment with thapsigargin which blocked caffeine- and muscarinic agonist-induced intracellular Ca^<2+> release. Muscarine was effective in increasing [Ca]_<in> in the presence of a desensitizing concentration of nicotine, and simultaneous addition of maximal doses of muscarine and nicotine caused an additive increase in [Ca]_<in>. On the other hand, nicotine-, ATP-, and high K^+-induced increase in [Ca]_<in> was markedly potentiated during continuous stimulation with muscarine. These results suggest that muscarine causes membrane depolarization by inhibiting M-current, which in turn increases Ca^<2+> influx passing through voltage-dependent Ca^<2+> channels.
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