| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
It has been discussed that the activities of transmitter receptors are modulated by extracellular divalent cations. In the present study, we examined the effects of divalent cations (Ca^<2+> and Zn^<2+>) on the GABAc receptor of the catfish retinal horizontal cells and the mouse bipolar cells. Currents were recorded from cultured cone-driven horizontal cells or isolated mouse bipolar cells using a whole cell clamp mode. In catfish retinal horizontal cells, when [Ca^<2+>]* was increased to 10 mM, IGABA was increased by 30 %, while it was reduced to 65 % when [Ca^<2+>]* was lowered to 0.1 mM.The concentration-response curves for IGABA in both 2.5 and 10 mM [Ca^<2+>]* were described with similar Hill coefficients (1.54 and 1.24) and EC_<50> values (3.0 and 3.1 muM). However, the amplitude of the saturation response in 10 mM [Ca^<2+>]* was greater than that in 2.5mM [Ca^<2+>]*. The inhibitory action of Zn^<2+> on the augmenting effect of [Ca^<2+>]* was non-competitive. It has been shown that [Ca^<2+>]* in the outer plexiform layer increases (-0.5 mM) when the retina is illuminated. In the dark, glutamate and Zn^<2+>, stored in photoreceptor terminals, are co-released and accumulate in the synaptic cleft between the photoreceptor and horizontal cells. Thus, these changes cooperatively modify the activity of GABAc receptors, and modulate the efficacy of the positive feedback mediated by GABAc autoreceptor. In isolated bipolar cells of the mouse retina, both GABAA and GABAG receptors were detected. High density GABAc receptor distribution was found at the axon terminal. Zn^<2+> inhibited GABAc receptors more strongly than the GABAALPHA receptors ; 1C_<50> for GABAc was 1.9 muM and that for GABAA was 67.4 muM.If Zn^<2+> is released from the bipolar cell terminal, it would suppress the recurrent inhibitory feedback from GABAergic amacrine cells to the bipolar cell terminal.
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