Hyperpolarization-activated cyclic nucleotide-gated channels preserve excitability in ON-bipolar cells after degeneration.

Retinal degeneration leads to extensive remodeling of inner retinal circuits following photoreceptor loss, but the intrinsic membrane properties of surviving bipolar cells remain incompletely understood. Here, we investigated the expression and functional contribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in ON-bipolar cells using the rd10 mouse model of retinitis pigmentosa. High-resolution fluorescence in situ hybridization showed no significant differences in Hcn1, Hcn2, and Hcn4 transcript levels between wild-type (WT) and rd10 bipolar cells. Whole-cell patch-clamp recordings detected hyperpolarization-activated inward currents consistent with Ih in both WT and rd10 ON-bipolar cells with no significant differences. In current-clamp recordings, the recovery of membrane potential following hyperpolarizing current pulses was significantly slowed by HCN channel blockers (ivabradine and ZD7288) in both genotypes. These findings indicate that HCN-sensitive conductances contribute to membrane potential recovery in ON-bipolar cells and remain detectable after photoreceptor degeneration.