Modulation by testosterone of an endogenous hERG potassium channel current

• Autorzy: Ridley J.M. , Shuba Y.M. , James A.F. , Hancox J.C.
• Języki publikacji: EN

Abstrakty

EN

hERG (human ether-a-go-go-related gene) potassium (K+) channels are expressed in a range of tissue types including neuroblastoma cells and the heart, in which hERG K+ current is important for action potential repolarization. Whilst gender differences in cardiac repolarization and the QT interval of the cardiac electrocardiogram are well-established, comparatively little is known about regulation of hERG channels by sex hormones. In this study, whole-cell patch-clamp recordings were made at 37 °C from SH-SY5Y human neuroblastoma cells to investigate modulation of endogenous hERG K+ channel current (IhERG) by testosterone. Acutely applied testosterone at a physiologically relevant concentration (10 nM) produced a modest (~13-15 %) increase in IhERG amplitude, whilst a high concentration (1 µM) slightly decreased IhERG. The stimulatory effect of testosterone was inhibited by the androgen receptor antagonist flutamide (10 µM) and the PI-3 kinase inhibitor wortmannin (1 µM). Chronic (24 h) application of testosterone also augmented IhERG via flutamide-sensitive receptor activation, without modulation of the current's voltage-dependence. These results demonstrate for the first time that testosterone can stimulate hERG K+ channels via activation of classical androgen receptors and implicate PI-3 kinase in the acute response.

Słowa kluczowe

EN

tumour tissue; neuronal tissue; testosterone; smooth muscle; cardiac repolarization; neuroblastoma cell; cardiac tissue; cardiac electrocardiogram; sex hormone; potassium channel; human ether-a-go-go-related gene; heart

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2008
• Tom: 59
• Numer: 3
• Opis fizyczny: p.395-407,fig.,ref.

Twórcy

autor

Ridley J.M.

• School of Medical Sciences The University of Bristol, Bristol, U.K.

autor

Shuba Y.M.

autor

James A.F.

autor

Hancox J.C.