Channelpedia

PubMed 19696788


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.1 , Kv1.2 , Kv1.3 , Kv1.5



Title: Kv1.1 and Kv1.3 channels contribute to the degeneration of retinal ganglion cells after optic nerve transection in vivo.

Authors: P D Koeberle, Y Wang, L C Schlichter

Journal, date & volume: Cell Death Differ., 2010 Jan , 17, 134-44

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19696788


Abstract
Degeneration of retinal ganglion cells (RGCs) - an important cause of visual impairment - is often modeled by optic nerve transection, which leads to apoptotic death of these central nervous system neurons. With this model, we show that specific voltage-gated K(+) channels (Kv1 family) contribute to the degeneration of rat RGCs and expression of apoptosis-related molecules in vivo. Retinal expression of Kv1.1, Kv1.2, Kv1.3 and Kv1.5 was examined by quantitative real-time reverse transcriptase-PCR and immunohistochemistry. Kv channel blockers and channel-specific short-interfering RNAs (siRNAs) were used to assess their roles in RGC degeneration. We found that (i) rat RGCs express Kv1.1, Kv1.2 and Kv1.3 (but not Kv1.5); (ii) intraocular injection of agitoxin-2 or margatoxin, potent blockers of Kv1.1, Kv1.2 and Kv1.3 channels, dose-dependently reduced the RGC degeneration; (iii) siRNAs applied to the cut optic nerve were rapidly transported throughout RGCs only, in which they reduced the expression of the cognate channel only. Our results show differential roles of the channels; siRNAs directed against Kv1.1 or Kv1.3 channels greatly reduced RGC death, whereas Kv1.2-targeted siRNAs had only a small effect, and siRNAs against Kv1.5 were without effect. (iv) Kv1.1 and Kv1.3 channels apparently contribute to cell-autonomous death of RGCs through different components of the apoptotic machinery. Kv1.1 depletion increased the antiapoptotic gene, Bcl-X(L), whereas Kv1.3 depletion reduced the proapoptotic genes, caspase-3, caspase-9 and Bad.