Carbenoxolone inhibition of voltage-gated Ca channels and synaptic transmission in the retina

We show that carbenoxolone, a drug used to block hemichannels in the retina to test the ephaptic model of horizontal cell inhibitory feedback, has strong inhibitory effects on voltage-gated Ca channels. Carbenoxolone ( 100 muM) reduced photoreceptor-to-horizontal cell synaptic transmission by 92%. Applied to patch-clamped, isolated cone photoreceptors, carbenoxolone inhibited Ca channels with an EC50 of 48 muM. At 100 muM, it reduced cone Ca channel current by 37%, reduced depolarization-evoked [Ca2+] signals in fluo-4 loaded retinal slices by 57% and inhibited Ca channels in Muller cells by 52%. A synaptic transfer model suggests that the degree of block of Ca channels accounts for the reduction in synaptic transmission. These results suggest broad inhibitory actions for carbenoxolone in the retina that must be considered when interpreting its effects on inhibitory feedback.