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Science 17 September 1999:
Vol. 285. no. 5435, pp. 1929 - 1931
DOI: 10.1126/science.285.5435.1929
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Reports

Acute Activation of Maxi-K Channels (hSlo) by Estradiol Binding to the beta  Subunit

Miguel A. Valverde, 1* Patricio Rojas, 2 Julio Amigo, 2 Diego Cosmelli, 2 Patricio Orio, 2 Maria I. Bahamonde, 2 Giovanni E. Mann, 4 Cecilia Vergara, 2 Ramon Latorre 23

Maxi-K channels consist of a pore-forming alpha  subunit and a regulatory beta  subunit, which confers the channel with a higher Ca2+ sensitivity. Estradiol bound to the beta  subunit and activated the Maxi-K channel (hSlo) only when both alpha  and beta  subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.

1 Departament de Ciències Experimentals i de la Salut, Universidad Pompeu Fabra, C/Doctor Aiguader 80, 08003 Barcelona, Spain.
2 Departmento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile, and Centro de Estudios Cientificos de Santiago, Casilla 16443, Santiago 9, Chile.
3 Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA 90095-1778, USA.
4 Centre for Cardiovascular Biology and Medicine, School of Biomedical Sciences, King's College London, London SE1 9RT, UK.
*   To whom correspondence should be addressed. E-mail: miguel.valverde{at}cexs.upf.es

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The C Terminus of the Human Nicotinic {alpha}4{beta}2 Receptor Forms a Binding Site Required for Potentiation by an Estrogenic Steroid.
K. Paradiso, J. Zhang, and J. H. Steinbach (2001)
J. Neurosci. 21, 6561-6568
   Abstract »    Full Text »    PDF »
Estrogen and Spermatogenesis.
L. O'Donnell, K. M. Robertson, M. E. Jones, and E. R. Simpson (2001)
Endocr. Rev. 22, 289-318
   Abstract »    Full Text »    PDF »
Role of estrogen in modulating EDHF-mediated dilations in the female rat middle cerebral artery.
E. M. Golding and T. E. Kepler (2001)
Am J Physiol Heart Circ Physiol 280, H2417-H2423
   Abstract »    Full Text »    PDF »
Animal Models Used in Identifying Gender-Related Differences.
B. B. Curry III (2001)
International Journal of Toxicology 20, 153-160
   Abstract »    PDF »
EETs relax airway smooth muscle via an EpDHF effect: BKCa channel activation and hyperpolarization.
C. Benoit, B. Renaudon, D. Salvail, and E. Rousseau (2001)
Am J Physiol Lung Cell Mol Physiol 280, L965-L973
   Abstract »    Full Text »    PDF »
Modulation of Potassium Current Characteristics in Human Myometrial Smooth Muscle by 17{beta}-Estradiol and Progesterone.
G. A. Knock, R. M. Tribe, A. A. Hassoni, and P. I. Aaronson (2001)
Biol Reprod 64, 1526-1534
   Abstract »    Full Text »
Maxi-K Potassium Channels: Form, Function, and Modulation of a Class of Endogenous Regulators of Intracellular Calcium.
V. K. Gribkoff, J. E. Starrett Jr., and S. I. Dworetzky (2001)
Neuroscientist 7, 166-177
   Abstract »    PDF »
Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms.
R. K. Dubey and E. K. Jackson (2001)
Am J Physiol Renal Physiol 280, F365-F388
   Abstract »    Full Text »    PDF »
The Phytoestrogen Genistein Produces Acute Nitric Oxide-Dependent Dilation of Human Forearm Vasculature With Similar Potency to 17{beta}-Estradiol.
H. A. Walker, T. S. Dean, T. A. B. Sanders, G. Jackson, J. M. Ritter, and P. J. Chowienczyk (2001)
Circulation 103, 258-262
   Abstract »    Full Text »    PDF »
17{beta}-Oestradiol acutely regulates Cl- secretion in rat distal colonic epithelium.
S. B Condliffe, C. M Doolan, and B. J Harvey (2001)
J. Physiol. 530, 47-54
   Abstract »    Full Text »    PDF »
Nongenomic actions of estrogens and xenoestrogens by binding at a plasma membrane receptor unrelated to estrogen receptor alpha and estrogen receptor beta.
A. Nadal, A. B. Ropero, O. Laribi, M. Maillet, E. Fuentes, and B. Soria (2000)
PNAS 97, 11603-11608
   Abstract »    Full Text »    PDF »
Estrogen Inhibition of Cystic Fibrosis Transmembrane Conductance Regulator-Mediated Chloride Secretion.
A. K. Singh, B. D. Schultz, J. A. Katzenellenbogen, E. M. Price, R. J. Bridges, and N. A. Bradbury (2000)
J. Pharmacol. Exp. Ther. 295, 195-204
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Potent inhibition of the aortic smooth muscle maxi-K channel by clinical doses of ethanol.
F. S. Walters, M. Covarrubias, and J. S. Ellingson (2000)
Am J Physiol Cell Physiol 279, C1107-C1115
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17-beta -Estradiol Modulation of Area Postrema Potassium Currents.
Z. Li and M. Hay (2000)
J Neurophysiol 84, 1385-1391
   Abstract »    Full Text »    PDF »
Effects of estrogen on cerebral blood flow and pial microvasculature in rabbits.
M. T. Littleton-Kearney, D. M. Agnew, R. J. Traystman, and P. D. Hurn (2000)
Am J Physiol Heart Circ Physiol 279, H1208-H1214
   Abstract »    Full Text »    PDF »
A Subset of Kappa Opioid Ligands Bind to the Membrane Glucocorticoid Receptor in an Amphibian Brain.
S. J. Evans, B. T. Searcy, and F. L. Moore (2000)
Endocrinology 141, 2294-2300
   Abstract »    Full Text »    PDF »


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