| Project/Area Number |
62570066
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Kurume University |
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Principal Investigator |
TOKIMASA Takayuki Kurume University School of Medicine Associate Professor, 医学部, 助教授 (50155511)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Toshihiko Kurume University School of Medicine Associate Professor, 医学部, 助手 (30172696)
有吉 護 久留米大学, 医学部, 助手 (50184297)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Muscarinic receptor / Second messenger / M-current / C-kinase / Calcium-activated potassium current / cyclic AMP / Ca^<2+>依存性K^+電流 / whole-cell clamp / H電流 / 細胞内ATP / adenylate cyclase / 交感神経節細胞 / 副交感神経節細胞 / 腸管神経節細胞 / アセチルコリン / 細胞内カルシウム / 神経細胞単離 / 細胞培養 |
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| Research Abstract |
Intracellular signal transduction mechanisms for muscarinic receptors were studied both in intact neurons and neurons in primary culture. Muscarine blocked two distinct potassium currents. One was the M-current (I(M)) and the other was a Calcium-activated potassium current (IK(CA)).
Protein Kinase-C and I(M). Bullfrog sympathetic neurons in primary culture were voltage-clamped in the whole-cell configulation. Muscarine induced I(M) inhibition was normally reversible but became irreversible when unhydrolzable GTP analogue GTP-gamma-S (10-30 muM) was present in a pipette solution. I(M) was blocked by a C-Kinase activator phorbol ester. Protein Kinase-A regulated a hyperpolarization-activated sodium/potassium current (H-current; I(H)) which was distinct from I(M) and was insensitive to muscarine. hydrolyzable from of ATP was necessary in a pipette solution both for I(M) and I(H). Essentially the same results were obtained from sensory neurons of bullfrogs and new born rats.
Cyclic AMP and IK(Ca). Muscarine blocked IK(Ca) in neurons within the enteric plexuses (non-cultured), where both I(M) and I(H) were non-existing. This was mediated by M-1 receptors and subsequent formation of cyclic AMP via G-protein coupled adenylate cyclase.
In summary, the followings can be concluded. The signal transduction for muscarinic receptors may occur at least in two ways in different neurons. One for I(M) via Protein Kinase-C and the other for IK(Ca) via cyclic AMP (and presumably protein Kinase-A).
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