Endothelin (Et-1) is an important paracrine vasoconstrictor, which is synthesized by the endothelium and stimulates increases in [Ca²⁺] and contraction in adjacent vascular myocytes. Electrophysiological studies have revealed that Et-1 promotes spontaneous transient depolarisations in retinal arterioles. These responses are mediated by Ca²⁺-activated Cl^– currents which can be blocked by niflumic acid and anthracene 9-carboxylate (Scholfield et al. 2006). In this study we tested the hypothesis that positive feedback via activation of Ca²⁺-sensitive Cl^– currents contributes to Et-1-induced Ca²⁺ signals. Male Sprague-Dawley rats (200-300g) were anaesthetized with CO₂ and killed by cervical dislocation. Retinae were rapidly removed and arterioles isolated mechanically. Vessel segments were incubated with fluo-4 AM, placed in an organ bath on an inverted microscope and superfused with physiological solutions at 37°C. High speed confocal imaging (20 fps) was used to record cellular Ca²⁺ signals and normalized fluorescence (F/F₀) was used as a measure of [Ca²⁺]. For each protocol, changes in mean fluorescence were recorded for 3 representative cells in each of 4 repeat experiments. Summary data are presented as mean±SEM. Et-1 alone (10nM) stimulated Ca²⁺ oscillations. Oscillation frequency was increased from 0.167±0.028 s^-1 under control conditions, to 0.342±0.036 s^-1 during the last 10 s in the presence of endothelin (P<0.01, non-parametric ANOVA). Oscillation amplitude (ΔF/F₀) was also increased from an average of 0.12±0.01 to 0.29±0.04 for control and Et-1 treatment periods, respectively (P<0.001). Baseline [Ca²⁺] was elevated, rising from a mean of 1.01±0.03 during the control period to 1.38±0.12 during Et-1 superfusion. Addition of the Cl^– channel blocker anthracene 9-carboxylate (10 mM) abolished the effects of Et-1 on oscillations. Oscillation frequency was decreased from 0.342±0.036 s^-1 at the end of the Et-1 treatment period, to 0.142±0.039 s^-1 when Et-1 and anthracene 9-carboxylate were both present (P<0.001). Similarly, mean oscillation amplitude was reduced from 0.29±0.04 in the presence of Et-1 to 0.13±0.02 when anthracene 9-carboxylate was also added (P0.05). In contrast, anthracene 9-carboxylate had no effect on the elevated baseline [Ca²⁺]. It appears, therefore, that activation of Ca²⁺-activated Cl^– currents plays an important role in the stimulation of Ca²⁺ oscillations by Et-1.