Effects of aldosterone on transient outward K + current density in rat ventricular myocytes

1 Aldosterone, a major ionic homeostasis regulator, might also regulate cardiac ion currents. Using the whole‐cell patch‐clamp technique, we investigated whether aldosterone affects the 4‐aminopyridine‐sensitive transient outward K + current ( I to1 ). 2 Exposure to 100 n m aldosterone for 48 h at 37 °C produced a 1.6‐fold decrease in the I to1 density compared to control myocytes incubated without aldosterone. Neither the time‐ nor voltage‐dependent properties of the current were significantly altered after aldosterone treatment. RU28318 (1 μ m ), a specific mineralocorticoid receptor antagonist, prevented the aldosterone‐induced decrease in I to1 density. 3 When myocytes were incubated for 24 h with aldosterone, concentrations up to 1 μ m did not change I to1 density, whereas L‐type Ca 2+ current ( I Ca,L ) density increased. After 48 h, aldosterone caused a further increase in I Ca,L . The delay in the I to1 response to aldosterone might indicate that it occurs secondary to an increase in I Ca,L . 4 After 24 h of aldosterone pretreatment, further co‐incubation for 24 h either with an I Ca,L antagonist (100 n m nifedipine) or with a permeant Ca 2+ chelator (10 μ m BAPTA‐AM) prevented a decrease in I to1 density. 5 After 48 h of aldosterone treatment, we observed a 2.5‐fold increase in the occurrence of spontaneous Ca 2+ sparks, which was blunted by co‐treatment with nifedipine. 6 We conclude that aldosterone decreases I to1 density. We suggest that this decrease is secondary to the modulation of intracellular Ca 2+ signalling, which probably arises from the aldosterone‐induced increase in I Ca,L . These results provide new insights into how cardiac ionic currents are modulated by hormones.