| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
The neurotransmitter GABA (gamma -aminobutyric acid) is involved in the inhibitory regulation of a variety of functions in the central nervous system. The receptors for GAGA comprise mainly GABA-A and GABA-B receptors. The GABA-A receptors has long a subject of intensive investigation and thus their structural and functional properties are now well understood. On the contrary, the role of GABA-B receptors still remains be elucidated. The purpose of this project was 1, to examine a modulatory role of GA B receptors on the function of voltage-gated calcium channels, and 2, to develop a model system in which functional GABA-B receptors can be expressed for electrophysiological analysis of GABA-B receptors. Regarding the first purpose, I have investigated the actions of GABA-B agonist, baclofen, on the High voltage activated (HVA)-calcium channels using patch clamp technique. The experimental results show that an activation of GABA-B receptors causes not only well-known inhibitory effect on the calcium cha opening, but also a transient augmentation of the HVA-calcium channel currents. suggested that this effect was probably mediated by a change in the intracellular se messenger system. Regarding the second purpose, I have established the model system that can be used as the expression system of GABA-B receptors. Cultured neurons of superior cervical ganglion provided a number of advantages, e.g., these cells are devoid inherent GABA-B receptors. By the microinjection technique of the mutated genes bined with the use of fluorescent GFP (green-fluorescent protein), exogenous mutated genes could be expressed in an identified cells of the culture disc.
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