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

1. Aldosterone, a major ionic homeostasis regulator, might also regulate ca rdiac ion currents. Using the whole-cell patch-clamp technique, we investig ated whether aldosterone affects the 4-aminopyridine-sensitive transient ou tward K+ current (I-tol). 2. Exposure to 100 nm aldosterone for 48 h at 37 degreesC produced a 1.6-fo ld decrease in the density compared to control myocytes incubated without a ldosterone. Neither the time- nor voltage-dependent properties of the curre nt were significantly altered after aldosterone treatment. RU28318 (1 mum), a specific mineralocorticoid receptor antagonist, prevented the aldosteron e-induced decrease in I-tol density. 3. When myocytes were incubated for 24 li with aldosterone, concentrations up to 1 mum did not change I-tol density, whereas L-type Ca2+ current (I-Ca ,I-L) density increased. After 48 h, aldosterone caused a further increase in I-Ca,I-L. The delay in the I-tol response to aldosterone might indicate that it occurs secondary to an increase in I-Ca,I-L. 4. After 24 h of aldosterone pretreatment, further co-incubation for 24 h e ither with an I-Ca,I-L antagonist (100 nm nifedipine) or with a permeant Ca 2+ chelator (10 muM BAPTA-AM) prevented a decrease in I-tol density. 5. After 48 h of aldosterone treatment, we observed a 2.5-fold increase in the occurrence of spontaneous Ca2+ sparks, which was blunted by co-treatmen t with nifedipine. 6. We conclude that aldosterone decreases I-tol density. We suggest that th is decrease is secondary to the modulation of intracellular Ca2+ Signalling , which probably arises from the aldosterone-induced increase in L-Ca,L-L. These results provide new insights into how cardiac ionic currents are modu lated by hormones.