Evaluation of Intrinsic Membrane Properties of Retinal Bipolar Cells in Photoreceptor–Deficient Mice

Abstract

Abstract: : Purpose: To evaluate the physiological function of retinal bipolar cells in L128 transgenic mice which show a rapid loss of photoreceptors due to the high expression of Y99CGCAP1, a mutant of guanylyl cyclase activating protein–1. Methods: Retinal neurons were isolated from L128 mice at the age of 2–16 months. Whole–cell patch–clamp recordings were performed on morphologically identified bipolar cells. Results: In L128 mice, apoptotic loss of rods and cones was accompanied by disappearance of the ERG a– and b–waves between two and three months of age. The inner retinal layers remained preserved in these mice long after all rods and cones had died, although the inner nuclear layer appeared more diffuse in the transgene–positive mice compared to their normal siblings. Despite some morphological abnormities which were observed in retinal neurons isolated from mice lacking all photoreceptors, both rod and cone bipolar cells could still be identified by their characteristic morphological features. Membrane depolarization evoked both low–voltage–activated T–type and high–voltage–activated L–type Ca²⁺ currents. The L–type Ca²⁺ currents in rod bipolar cells still appeared to be located only at the axon terminals. Membrane depolarization also evoked voltage–dependent outward K⁺ currents. Membrane hyperpolarization evoked inwardly rectifying K⁺ currents and/or h–currents. Furthermore, both rod and cone bipolar cells were capable of generating spontaneus regnerative activities similar to those obseved in bipolar cells in normal mice. Conclusions: Our results suggest that retinal bipolar cells in the photoreceptor–deficient retina retain their functional voltage–dependent membrane channels.

Keywords: bipolar cells • electrophysiology: non–clinical • degenerations/dystrophies