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 nM aldosterone for 48 h at 37 degrees 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 microM), 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 microM 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 nM nifedipine) or with a permeant Ca(2+) chelator (10 microM 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.
Bénitah
J P
JP
Laboratoire de Physiopathologie Cardiovasculaire, INSERM U-390, IFR3, CHU Arnaud de Villeneuve, 34295 Montpellier, France. benitah@welchlink.welch.jhu.edu
Perrier
E
E
Gómez
A M
AM
Vassort
G
G
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D004553:Electric Conductivity; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone