FURUKAWA Tetsuo Research Associate, Kyushu Inst. of Tech., 情報工学部, 助手 (50219101)
DJAMGOZ M.b.a. Senior Tutor, Imperial College, London, インペリアルカレッジ・生物学科, 教授
YAMADA Masahiro Adjunct Prof., Univ. of Tsukuba, 生物科学系(併任), 教授
This research is concerned with synaptic transmission from cone photoreceptors to H1 type horizontal cells (H1 HCs) in the cyprinid fish retina. The synapse had long been thought to be of the glutamate-driven non-NMDA channel type. Since several years ago, our Japan-UK group has been revising this notion with respect to the synaptic transmission for short-wavelength signals ; our set of evidence shows that the synapse made by blue and/or green cones is of a conductance-decreasing and polarity-reversing type with APB (2-amino-4-phosphonobutyrate) as an agonist.
There remain two major subjects to be explored about the APB synapse, namely, the role in visual function and the underlying molecular mechanisms. This year, our international team was able to make considerable progress to this end. First, it was found by input-resistance measurement that the short-wavelength synaptic transmission is blocked reversely by dark adaptation, and that the site of the blocking action is postsynaptic. It has become evident, therefore, that the synapse operates with plasticity as a function of stimulus wavelength and light/dark retinal adaptation. Furthermore, another series of our experiments showed that the synapse with these properties subserves wavelength- and adaptation-dependent control on the receptive field size of H1 HCs. To account for this effect quantitatively, we are currently developing a nonlinear version of the cable-theory model of the H1 HC syncitium in which the membrane resistance is variable as opposed to the constant gap-junctional resistance.
In order to elucidate the molecular mechanisms underlying the synapse in question, we carried out certain experiments involving intracellular injection of cGMP and superfusion with nitroprusside. The results so far indicate that the synaptic mechanism is metabotropic, involving G-protein*PDE*cGMP, and/or Ca^<2+>* NOS*NO*GC*cGM in the course from APB receptor to the channel gating.