| Project/Area Number |
09044296
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
KURACHI Yoshihisa Osaka University, Faculty of Medicine, Professor, 医学部, 教授 (30142011)
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| Co-Investigator(Kenkyū-buntansha) |
INANOBE Atsushi Osaka University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00270851)
HORIO Yoshiyuki Osaka University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30181530)
CLAPHAM David E. Harvard Medical School, Professor, 医学部, 教授
YAMADA Mitsuhiko Osaka University, Faculty of Medicine, Assistant Professor (10263237)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ion chanel / inward rectifier / G protein / dopaminergic neuron / hormone secretion / pituitary / substantia nigra / neuron |
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| Research Abstract |
Activation of neuronal G protein-gated inwardly rectifying K+^+ (K_G) channels causes the formation of slow inhibitory postsynaptic potentials. Current opinion suggests that neuronal K_G channels are heterotetramers of Kir3.1 and Kir3.2, however there are several splicing variants of Kir3.1 and Kir3.2, and another subunit of Kir3.3 in the brain. Theoretically there might be so many diverse K_G channel assemblies composed of these subunits, however little knowledges are available for such diversification and physiological function of neuronal K_G channels. In substantia nigra (SN), K_G channel was an assembly of Kir3.2a and Kir3.2c. In this assembly, the former subunit is primarily responsible for formation of a functional K_G channel, and the latter controls subucellular localization of the K_G channel. Therefore, Kir3.2 splicing variants play distinct roles in the heteromeric assembly of the K_G channel in dopaminergic neurons of SN.When we studied about the distribution of K_G channels in the anterior pituitary lobe that we found K_G channel subunits Kir3.1 and Kir3.4 to be localized upon the membranes of intracellular dense core vesicles which contained TSH.TRH treatment provoked the translocation of these subunits to the plasma membrane and markedly enhanced K_G currents stimulated by dopamine and somatostatin. These data indicates a novel mechanism for the rapid insertion of functional ion channels into the plasma membrane, which could form a new type of negtive feedback control loop for hormone secretion in the endocrine system.
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