Electrophysiological recordings in retinal arterioles have demonstrated that application of endothelin promotes Ca²⁺-sensitive, spontaneous transient inward and outward currents (Scholfield et al, 2007). The present study provides evidence that these currents act as important feedback mechanisms, modulating endothelin induced Ca²⁺-signals. Retinal arterioles mechanically isolated from male Sprague-Dawley rats were loaded with fluorescent Ca²⁺-indicator by incubation with fluo-4 AM (5 µM). Loaded vessels were placed in an organ bath on an inverted microscope and superfused with physiological solutions at 37^oC. High-speed confocal imaging (20 fps) was used to record cellular Ca²⁺-signals from arteriolar myocytes. Normalized fluorescence (F/F₀) was calculated as a measure of [Ca²⁺]. Ca²⁺-oscillations were stimulated when endothelin (Et1, 10nM) was added. Oscillation frequency was increased from 0.123±0.018 s^-1 (mean±SEM) under control conditions, to 0.340±0.021 s^-1 in the presence of Et1 (N=89 cells in 4 vessels from 4 animals; P<0.001, non-parametric ANOVA, Dunn’s multiple comparison post-hoc test). Oscillation amplitude (ΔF/F₀) was also increased from an average of 0.28±0.02 to 0.57±0.03 for control and Et1 treatment periods, respectively (P<0.001). We have previously shown that 4,4′- diisothiocyanatostilbene-2,2′-disulphonic acid (DIDS) inhibits a Ca²⁺-activated Cl^–-conductance in these cells (McGahon et al, 2008). Addition of DIDS (1mM) in the continued presence of Et1 reduced the mean frequency of Ca²⁺-oscillations back to control values (0.062±0.001 s^-1; P<0.001 vs Et1 alone; NS vs Control). DIDS also reduced the mean amplitude of the Ca²⁺-oscillations to 0.40±0.04, but this was not statistically significantly different from the amplitude in the presence of ET1 alone. Iberiotoxin (100 nM), an inhibitor of large-conductance Ca²⁺-activated K⁺-channels, exaggerated the effects of Et1. Oscillation amplitude was increased from 0.24±0.01 in the presence of Et1 alone, to 0.33±0.02 when iberiotoxin was also added (N=51 cells in 4 vessels from 4 animals; P<0.001). Iberiotoxin, however, had no additional effect on oscillation frequency. It appears, therefore, that Ca²⁺-activated Cl^– currents play an important role in determining the frequency of the Ca²⁺-oscillations elicited by endothelin, while Ca²⁺-activated K⁺-currents limit the amplitude of these oscillations.