Modulation of I(A) potassium current in adrenal cortical cells by a series of ten lanthanide elements
Por:
Enyeart J.J., Xu L., Gomora J.C., Enyeart J.A.
Publicada:
1 ene 1998
Resumen:
The modulation of I(A) K+ current by ten trivalent lanthanide (Ln3+) cations spanning the series with ionic radii ranging from 0.99 Å to 1.14 Å was characterized by the whale-cell patch clamp technique in bovine adrenal zona fasciculata (AZF) cells. Each of the ten Ln3+s reduced I(A) amplitude measured at +20 mV in a concentration-dependent manner. Smaller Ln3+s were the most potent and half-maximally effective concentrations (EC50) varied inversely with ionic radius for the larger elements, Estimation of EC50s yielded the following potency sequence: LU3+ (EC50 = 3.0 ?M) ~ Yb3+ (EC50 = 2.7 ?M) > Er3+(EC50 = 3.7 ?M) ? Dy3+ (EC50 = 4.7 ?M) > Gd3+ (EC50 = 6.7 ?M) ~ Sm3+ (EC50 = 6.9 ?M)> Nd3+ (EC50 = 11.2 ?M) > Pr3+ (EC40 = 22.3 ?M) > Ce3+ (EC50 = 28.0 ?M) > La3+ (EC50 = 33.7 ?M). Ln3+s altered selected voltage-dependent gating and kinetic parameters of I(A) with a potency and order of effectiveness that paralleled the reduction of I(A) amplitude. Ln3+s markedly slowed activation kinetics and shifted the voltage-dependence of I(A) gating such that activation and steady-state inactivation occurred at more depolarized potentials. In contrast, Ln3+s did not measurably alter inactivation or deactivation kinetics and only slightly slowed kinetics of inactivated channels returning to the closed state. Replacement of external Ca2+ with Mg2+ had no effect on the concentration-dependent inhibition of I(A) by Ln3+s. In contrast to their action on I(A) K+ current, Ln3+s inhibited T-type Ca2+ currents in AZF cells without slowing activation kinetics. These results indicate that Ln3+ modulate I(A) K+ channels through binding to a site on I(A) channels located within the electric field but which is not specific for Ca2+. They are consistent with a model where Ln3+ binding to negative charges on the gating apparatus alters the voltage-dependence and kinetics of channel opening. Ln3+s modulate transient K+ and Ca2+ currents by two fundamentally differnt mechanisms.
Filiaciones:
Enyeart J.J.:
Department of Pharmacology, Ohio State Univ. College of Medicine, 5188 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210-1239, United States
Neuroscience Program, Ohio State University, College of Medicine, Columbus, OH 43210-1239, United States
Xu L.:
Department of Pharmacology, Ohio State Univ. College of Medicine, 5188 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210-1239, United States
Gomora J.C.:
Department of Pharmacology, Ohio State Univ. College of Medicine, 5188 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210-1239, United States
Enyeart J.A.:
Department of Pharmacology, Ohio State Univ. College of Medicine, 5188 Graves Hall, 333 W. 10th Ave., Columbus, OH 43210-1239, United States
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