A Receptor-Independent Effect of Estrone Sulfate on the hERG Channel

Shoko Kakusaka; Mahoko Asayama; Asami Kaihara; Tetsuo Sasano; Takeshi Suzuki; Junko Kurokawa; Tetsushi Furukawa

doi:10.1254/jphs.08257sc

Journal of Pharmacological Sciences (Jan 2009)

A Receptor-Independent Effect of Estrone Sulfate on the hERG Channel

Shoko Kakusaka,
Mahoko Asayama,
Asami Kaihara,
Tetsuo Sasano,
Takeshi Suzuki,
Junko Kurokawa,
Tetsushi Furukawa

Affiliations

Shoko Kakusaka: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan
Mahoko Asayama: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; Mitsubishi Tanabe Pharma Corporation, Safety Research Division, Kisarazu, Chiba 292-0818, Japan
Asami Kaihara: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Tetsuo Sasano: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan
Takeshi Suzuki: Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan
Junko Kurokawa: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; Corresponding author. [email protected]
Tetsushi Furukawa: Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan

DOI: https://doi.org/10.1254/jphs.08257sc
Journal volume & issue: Vol. 109, no. 1
pp. 152 – 156

Abstract

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We recently reported that physiological concentrations of 17β-estradiol partially down-regulate cardiac rapidly-activating delayed rectifier K+ currents (hERG currents) independently of estrogen-receptor signaling. To determine if other estrogens have the same effect as that of 17β-estradiol, we investigated receptor-independent effects of estrone, estrone 3-sulfate, and estriol on hERG currents in patch-clamped estrogen-negative HEK293 cells. Only estrone 3-sulfate partially suppressed hERG currents in a receptor-independent manner by modifying the gating. The concentration-dependence of estrone 3-sulfate revealed that physiological levels of circulating estrone 3-sulfate can modulate hERG currents to the maximal extent in both women and men at any age. Keywords:: estrogen, K+ channel (hERG), heart

Published in Journal of Pharmacological Sciences

ISSN: 1347-8613 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/journal-of-pharmacological-sciences

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