| First Author | Zanetti L | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 2732 |
| PubMed ID | 33526839 | Mgi Jnum | J:309964 |
| Mgi Id | MGI:6512829 | Doi | 10.1038/s41598-021-82210-7 |
| Citation | Zanetti L, et al. (2021) Function of cone and cone-related pathways in CaV1.4 IT mice. Sci Rep 11(1):2732 |
| abstractText | CaV1.4 L-type calcium channels are predominantly expressed in photoreceptor terminals playing a crucial role for synaptic transmission and, consequently, for vision. Human mutations in the encoding gene are associated with congenital stationary night blindness type-2. Besides rod-driven scotopic vision also cone-driven photopic responses are severely affected in patients. The present study therefore examined functional and morphological changes in cones and cone-related pathways in mice carrying the CaV1.4 gain-of function mutation I756T (CaV1.4-IT) using multielectrode array, patch-clamp and immunohistochemical analyses. CaV1.4-IT ganglion cell responses to photopic stimuli were seen only in a small fraction of cells indicative of a major impairment in the cone pathway. Though cone photoreceptors underwent morphological rearrangements, they retained their ability to release glutamate. Our functional data suggested a postsynaptic cone bipolar cell defect, supported by the fact that the majority of cone bipolar cells showed sprouting, while horizontal cells maintained contacts with cones and cone-to-horizontal cell input was preserved. Furthermore a reduction of basal Ca(2+) influx by a calcium channel blocker was not sufficient to rescue synaptic transmission deficits caused by the CaV1.4-IT mutation. Long term treatments with low-dose Ca(2+) channel blockers might however be beneficial reducing Ca(2+) toxicity without major effects on ganglion cells responses. |
