Abstract
Purpose: :
Reciprocal feedback from A17 amacrine cells to rod bipolar cells (A17 feedback) has been extensively studied morphologically and in in vitro preparations using pharmacological agents like GABAc antagonists. In particular, it has been elucidated that the large-conductance Ca2+-activated K+ (BK) channel plays a pivotal role for the A17 feedback modulating GABA release from A17s (Grimes et al., Nat Neurosci 2009). Here, we show for the first time functional evidence for A17 feedback in vivo based on a genetically engineered mouse model lacking BK channels using electroretinography (ERG).
Methods: :
For this work, Bk knockout mice (Sausbier et al., PNAS 2004) and wild type littermates were examined with Ganzfeld ERG (Multiliner Vision, VIASYS, Germany). Single flash ERG responses were obtained under both scotopic and photopic conditions. The study was performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Results: :
Under scotopic conditions, the lack of BK channels had no substantial effect on photoreceptor output at all intensities examined, suggesting that these channels do not alter rod ON bipolar cell input. In line with this result, the signals attributed to rod ON bipolar cells in the Bk knockouts were not different from those in wild type mice at low stimulus intensities. However, at intermediate stimulus intensities close to rod system saturation, a marked reduction of rod ON bipolar cell output was present in Bk-/- mice. At high intensities much above normal rod saturation threshold, the flash ERG responses in Bk knockout mice were again comparable to those in wild type mice. Also, under photopic conditions, no obvious functional alteration was detected.
Conclusions: :
These findings demonstrate that BK channels do modulate visual responses in vivo at intermediate lighting conditions. Our data are in support of the hypothesis that A17 feedback on rod bipolar cells helps to expand the dynamic range of the rod system.
Keywords: electroretinography: non-clinical • retinal connections, networks, circuitry • signal transduction: pharmacology/physiology