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Modulation by testosterone of an endogenous hERG potassium channel current

100%

Ridley J. M., Shuba Y. M., James A. F., Hancox J. C.

Journal of Physiology and Pharmacology

2008

tom 59

nr 3

395-407

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.

BDNF and NT-3 widen the scope of neurotrophin activity: Pharmacological implications

100%

Skup M. H.

Acta Neurobiologiae Experimentalis

1994

tom 54

nr 2

Ograniczanie wyników

1 Acta Neurobiologiae Experimentalis

1 Journal of Physiology and Pharmacology

1 Hancox J. C.

1 James A. F.

1 Ridley J. M.

1 Shuba Y. M.

1 Skup M. H.

1 2008

1 1994

Wyniki wyszukiwania

Modulation by testosterone of an endogenous hERG potassium channel current

BDNF and NT-3 widen the scope of neurotrophin activity: Pharmacological implications