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O Strauss, H Heimann, G Martin, H Agostini, LL Hansen, R Rosenthal, MH Foerster; Increased activity of L-type Ca2+ Channels in RPE Cells Isolated from Choroidal Neovascular Membranes from Patients With Age-related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):684.
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Purpose: Since RPE cells in choroidal neovascular (CNV) membranes secrete the majority of angiogenic factors these cells play a central role in the induction of subretinal angiogenesis in age-related macular degeneration. We could identify the L-type Ca2+ channel in RPE cells as a subtype known to be involved in the regulation of secretion (Strauss et al. 2000). Purpose of the study is to analyze the activity and regulation of L-type channels in RPE cells from CNV membranes. Methods: Perforated-patch clamp recordings of Ba2+ currents through L-type channels were performed with freshly isolated and cultured RPE cells from CNV membranes isolated from AMD patients after eye surgery. Data are given as mean ± SEM. Results: Freshly isolated and cultured cells showed nifedipine-sensitive inward currents with electrophysiological properties of L-type channels. The freshly isolated cells showed with 9.28 ± 7 pApF-1 (n = 3) and the cultured cells with 3.9 ± 0.2 pApF-1 (n = 10) an increased density of the maximal current amplitude (cells from healthy donors: 0.96 ± 0.11 pApF-1, n = 8). In addition, L-type currents in freshly isolated cells displayed steady-state activation which is shifted towards more negative potentials (V1/2 = -18 mV versus V1/2 = -12 mV). Inhibition of tyrosine kinase by lavendustin A (10µM) lead in both freshly isolated and cultured cells to an increase in the maximal current amplitude (fresh cells to 109 ± 7 %, n = 2; cultured cells to 124.8 ± 5 %, n = 10). In cultured cells from healthy donors application of lavendustin A lead to a reduction in the maximal current amplitude to 79 ± 5 % (n = 4). Conclusion: For the first time, freshly isolated and cultured RPE cells from CNV membranes have been studied with cell physiological methods. These cells showed increased activity and facilitated activation of L-type channels due to a changed regulation by tyrosine kinase. We conclude that increased secretory activity of RPE cells in CNV membranes is accompanied by increased activity of Ca2+ channels which are to be involved in the regulation of secretion.
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