Abstract
Purpose: :
T-type Ca channels have been known to play an important role in many neural functions. Three isoforms of T-type Ca channels, α1G (Cav3.1), α1H (Cav3.2), and α1I (Cav3.3), have been cloned and characterized. Previous studies have reported the presence of T-type Ca currents in retinal neurons, including retinal bipolar cells. However, the expression patterns of T-type Ca channels in the retina remain unknown. Whether T-type Ca channels play a functional role in retinal signal processing also remains unclear. In this study, using α1H-deficient mice we investigated the expression and potential functions of the α1H T-type Ca channel in the retina.
Methods: :
The expression of the α1H Ca channel in the retina was investigated by immunostaining. T-type Ca currents were recorded in the whole-cell configuration in retinal slices. The morphology of the recorded cells was identified by dye filling through recording electrodes. Optokinetic reflex was examined using a computer-driven virtual optomotor system. Retinal directional selectivity was assessed by multi-electrode recordings. The directional selectivity index (DSI) was calculated as: DSI = (Preferred peak frequency - Null peak frequency)/(Preferred peak frequency + Null peak frequency).
Results: :
A subpopulation of type-3 cone bipolar cells was stained with an antibody specific for the α1H Ca channel. The specificity of the antibody was confirmed by the absence of the staining in α1H-deficient mice. Consistently, most of the recorded type-3 cone bipolar cells displayed a marked decrease in T-type Ca currents in α1H-deficient mice. The average peak T-type Ca currents in wild-type and α1H-deficient mice were 74.5 ± 32.7 (mean ± SD; n = 37) and 39.7 ± 28.3 (n = 9), respectively. No optokinetic reflex could be elicited in α1H-deficient mice. The directional selectivity indexes of the cells located in the ganglion cell layer were all significantly decreased. The largest decrease was observed in OFF cells. The average DSI of OFF cells in wild-type and α1H-deficient mice were 0.27 ± 0.03 (mean ± SE; 47 cells) and 0.17 ± 0.02 (52 cells), respectively.
Conclusions: :
The results of this study show that the α1H Ca channel is expressed in a subpopulation of type-3 cone bipolar cells. In addition, α1H-deficient mice display a deficit in the optokinetic reflex and a significant decrease in retinal directional selectivity. Our results suggest that the α1H T-type Ca channel may play a role in retinal directional selectivity.
Keywords: ion channels • transgenics/knock-outs • retina: proximal (bipolar, amacrine, and ganglion cells)