The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Nontranscriptional Regulation of Cardiac Repolarization Currents by Testosterone
Open accessAbstract
Background— Women have longer QT c intervals than men and are at greater risk for arrhythmias associated with long QT c intervals, such as drug-induced torsade de pointes. Recent clinical and experimental data suggest an important role of testosterone in sex-related differences in ventricular repolarization. However, studies on effects of testosterone on ionic currents in cardiac myocytes are limited. Methods and Results— We examined effects of testosterone on action potential duration (APD) and membrane currents in isolated guinea pig ventricular myocytes using patch-clamp techniques. Testosterone rapidly shortened APD, with an EC 50 of 2.1 to 8.7 nmol/L, which is within the limits of physiological testosterone levels in men. APD shortening by testosterone was mainly due to enhancement of slowly activating delayed rectifier K + currents ( I Ks ) and suppression of L-type Ca 2+ currents ( I Ca,L ), because testosterone failed to shorten APD in the presence of an I Ks inhibitor, chromanol 293B, and an I Ca,L inhibitor, nisoldipine. A nitric oxide (NO) scavenger and an inhibitor of NO synthase 3 (NOS3) reversed the effects of testosterone on APD, which suggests that NO released from NOS3 is responsible for the electrophysiological effects of testosterone. Electrophysiological effects of testosterone were reversed by a blocker of testosterone receptors, a c-Src inhibitor, a phosphatidylinositol 3-kinase inhibitor, and an Akt inhibitor. Immunoblot analysis revealed that testosterone induced phosphorylation of Akt and NOS3. Conclusions— The nontranscriptional regulation of I Ks and I Ca,L by testosterone is a novel regulatory mechanism of cardiac repolarization that can potentially contribute to the control of QT c intervals by androgen.
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Mechanistic Pathways of Sex Differences in Cardiovascular Disease
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Gender Differences in Clinical Manifestations of Brugada Syndrome
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Michels, G., & Hoppe, U. C. (2008) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.08.004 · Cited by 198
Nakamura, H., Kurokawa, J., Bai, C.-X., Asada, K., Xu, J., Oren, R. V., Zhu, Z. I., Clancy, C. E., Isobe, M., & Furukawa, T. (2007) · Circulation · doi:10.1161/circulationaha.107.702407 · Cited by 190
Self-citation
Metadata
- Authors
- Bai, C.-X., Kurokawa, J., Tamagawa, M., Nakaya, H., & Furukawa, T.
- Venue
- Circulation
- Published
- 2005-09-20
- Volume
- 112
- Issue
- 12
- Pages
- 1701-1710
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2006973263
- Cited by
- 254
- References
- 41
- FWCI
- 7.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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