Involvement of CGRP receptors in retinal spreading depression

•Retinal spreading depression is an efficient in vitro model of migraine for assessing anti-migraine drugs targeting CGRP receptors. CALCRL is expressed in the chick retina•CGRP receptors are involved in retinal spreading depression.

BackgroundCortical spreading depression (CSD) is a transient propagating excitation of synaptic activity followed by depression, which is implicated in migraine with aura and is regarded as the underlying cause of migraine. Calcitonin-gene related peptide (CGRP) receptors play a crucial role in mediating the magnitude of CSD in rat cortical slice. This study aimed to examine whether CGRP receptors are involved in retinal spreading depression (RSD) in chicks.MethodsWestern blot was used for detection of calcitonin-receptor like receptor (CALCRL) and intrinsic optical imaging was used for pharmacological investigation.ResultsWe found that the key component of CGRP receptor, CALCRL, is expressed in the chick retina. Using an in vitro migraine RSD model, we demonstrated that BIBN4096, a potent antagonist for CGRP receptors, markedly reduced the magnitude of RSD induced by K+, but also the propagation rate.ConclusionsThe data suggest that CGRP receptors mediate RSD propagation involving neuronal mechanism and approve that RSD is an efficient in vitro approach for assessing anti-migraine drugs targeting CGRP receptors.