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 microM) reduced photoreceptor-to-horizontal cell synaptic transmission by 92%. Applied to patch-clamped, isolated cone photoreceptors, carbenoxolone inhibited Ca channels with an EC(50) of 48 microM. At 100 microM, it reduced cone Ca channel current by 37%, reduced depolarization-evoked [Ca(2+)] signals in fluo-4 loaded retinal slices by 57% and inhibited Ca channels in Müller 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.
Vessey
John P
JP
Department of Physiology and Biophysics, Dalhousie University, 5859 University Ave., Halifax, Nova Scotia B3H-4H7, Canada.
Lalonde
Melanie R
MR
Mizan
Hossein A
HA
Welch
Nicole C
NC
Kelly
Melanie E M
ME
Barnes
Steven
S
D000557:Ambystoma / Q000254:growth & development; D000814:Aniline Compounds; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002229:Carbenoxolone / Q000494:pharmacology*; D004594:Electrophysiology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D007814:Larva; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014966:Xanthenes
D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C409648:Fluo 4; D005456:Fluorescent Dyes; D014966:Xanthenes; D002229:Carbenoxolone