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H. Heikkinen, F. Vinberg, S. Nymark, A. Koskelainen; Blocking Rod-Cone Gap Junctions Mimics Effects of Light on Mouse Cone Erg. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3292.
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© ARVO (1962-2015); The Authors (2016-present)
Cone-driven a- and b-waves of rodent and primate ERG grow up to 2-fold during first minutes under steady background light. The growth in a-wave is independent of glutaminergic transmission1. We examined the possibility of light-induced modulation in rod-cone gap junctional (GJ) coupling as a source of this phenomenon.
Preflash-isolated mouse cone responses to 532 nm flashes in dark-adapted state or under steady backgrounds (IB) were recorded with transretinal ERG. 2mM aspartate or 20µM APB + 10µM NBQX were added to suppress synaptic transmission. Preflash-stimulus pairs were delivered either at long intervals, allowing both rods and cones to recover between pairs, or at <1 sec intervals, allowing only cones to recover.
Light increased a- and b-waves similarly as in vivo. In isolated photoresponses, the initial 5-10 ms was not affected, while the maximum amplitude grew in proportion to IB. The recovery phase of the responses was generally fastened. Mild enhancement was initiated already at IB of ca. 30 P*s-1 per cone, and half-maximal growth was achieved at ca. 300 P*s-1 (producing 1600 R*s-1 in rods), a level not expected to light-adapt the cone phototransduction machinery. The steady state cone amplitudes scaled linearly with the level of rod suppression. At fully rod-saturating backgrounds further increase of IB decreased steady state cone responses. The cone enhancement could also be induced with flash trains maintaining rods in saturation while allowing cones to recover between flashes.Three structurally unrelated GJ blockers, carbenoxolone (100µM), meclofenamic acid (MFA, 50µM) and octanol (OCT, 1mM), caused similar changes as background light in dark-adapted cone flash responses. They also prevented cone response growth with background illumination, revealing prototypical flash response desensitization (sensitivity-halving background 5000±1000 P*s-1) and acceleration with background light. MFA and OCT had no harmful effects on cone sensitivity or kinetics, and their effects were reversible.
The results suggest that cone responses are suppressed by rods through gap junctional coupling, and that this coupling is gradually weakened with rod saturation under mesopic backgrounds. This would allow rods to connect to cone pathways in dark-adapted retina but not let rod hyperpolarization to affect cone function in photopic conditions.1Bui & Fortune (2006), Vis. Neurosci. 23:155-67
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