Normal photoresponses and altered b-wave responses to APB in the mdx(Cv3) mouse isolated retina ERG supports role for dystrophin in synaptic transmission
التفاصيل البيبلوغرافية
العنوان:
Normal photoresponses and altered b-wave responses to APB in the mdx(Cv3) mouse isolated retina ERG supports role for dystrophin in synaptic transmission
ThemdxCv3mouse is a model for Duchenne muscular dystrophy (DMD). DMD is an X-linked disorder with defective expression of the protein dystrophin, and which is associated with a reducedb-wave and has other electro- retinogram (ERG) abnormalities. To assess potential causes for the abnormalities, we recorded ERGs from pieces of isolated C57BL/6J andmdxCv3mouse retinas, including measurements of transretinal and intraretinal potentials. The ERGs from the isolatedmdxCv3retina differ from those of control retinas in that they show reducedb-wave amplitudes and increasedb-wave implicit times. Photovoltages obtained by recording across the photoreceptor outer segments of the retinas did not differ from normal, suggesting that the likely causes of the reducedb-wave are localized to the photoreceptor to ON-bipolar synapse. At a concentration of 50 μM, the glutamate analog DL-2-amino-4-phosphonobutyric acid (APB) blocks theb-wave component of the ERG, by binding to sites on the postsynaptic membrane. The On-bipolar cell contribution to the ERG was inferred by extracting the component that was blocked by APB. We found that this component was smaller in amplitude and had longer response latencies in themdxCv3mice, but was of similar overall time course. To assess the sensitivity of sites on the postsynaptic membrane to glutamate, the concentration of APB in the media was systematically varied, and the magnitude of blockage of the light response was quantified. We found that themdxCv3retina was 5-fold more sensitive to APB than control retinas. The ability of lower concentrations of APB to block theb-wave inmdxCv3suggests that the ERG abnormalities may reflect alterations in either glutamate release, the glutamate postsynaptic binding sites, or in other proteins that modulate glutamate function in ON-bipolar cells.