Endocrine Abstracts (2004) 7 P63

Testosterone inhibits Ca2+ currents in A7r5 vascular smooth muscle cells, and in HEK293 cells stably expressing the alpha1C subunit of L-type Ca2+ channels (CaV1.2) and alpha1H T-type Ca2+ channels (CaV3.2)

JL Scragg1, RD Jones2, KC Channer3, TH Jones2 & C Peers1


1Institute for Cardiovascular Research, The University of Leeds, Leeds, UK; 2Hormone & Vascular Biology Group, Academic Unit of Endocrinology, The University of Sheffield, Sheffield, UK; 3Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK.


Testosterone reduces myocardial ischaemia in men with coronary artery disease (CAD) and improves symptoms and exercise capacity in men with congestive heart failure (CHF), effects proposed to be due to testosterone-induced vasodilatation. Isolated vessel studies suggest this occurs via a calcium antagonistic action upon voltage-gated Ca2+ channels but this has yet to be investigated directly.

We therefore employed patch clamp methodology to study the effect of testosterone (10-9-10-6M) upon whole-cell Ca2+ channel currents (using 2x10-3M Ba2+ as the charge carrier), initially in A7r5 vascular smooth muscle cells and then in HEK293 cells stably expressing either the main pore-forming alpha1C subunit of a human L-type Ca2+ channel (CaV1.2), or alpha1H T-type Ca2+ channels (CaV3.2).

Testosterone (10-9-10-6M) caused a rapid, irreversible concentration-dependent inhibition of Ca2+ currents in A7r5 vascular smooth with an IC50 of 7.21plus/minus0.06x10-8M. A similar inhibitory effect was observed in HEK 293 cells expressing the alpha1C L-type Ca2+ channel subunit, producing an IC50 of 6.10plus/minus0.06x10-8M. Current-voltage relationships indicated that testosterone caused a similar inhibition at all activating potentials, suggesting that the inhibition was voltage-independent. Testosterone (10-9-10-6M) also inhibited Ca2+ currents in HEK293 cells expressing alpha1H T-type Ca2+ channels, but this effect was partially reversible with a lower IC50 of 2.31plus/minus0.007x10-7M.

Testosterone inhibits Ca2+ currents in A7r5 cells and in HEK293 cells stably expressing the main pore-forming alpha1C subunit of L-type Ca2+ channels with a similar efficacy and potency, demonstrating that testosterone acts as an inhibitor of L-type voltage-gated Ca2+ channels in vascular smooth muscle, via interaction with the alpha1C subunit. Significantly this inhibition occurred at concentrations approaching those found physiologically. Testosterone also inhibits T-type voltage-gated Ca2+ channels, which are also expressed in vascular smooth muscle, but with a lower potency. This calcium antagonistic action may contribute to the clinical benefits associated with testosterone therapy in men with CAD and CHF.

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