Impact of testosterone on cardiac L-type calcium channels and Ca(2+) sparks: Acute actions antagonize chronic effects

Item Type:	Article
Title:	Impact of testosterone on cardiac L-type calcium channels and Ca(2+) sparks: Acute actions antagonize chronic effects
Creators Name:	Er, F. and Michels, G. and Brandt, M.C. and Khan, I. and Haase, H. and Eicks, M. and Lindner, M. and Hoppe, U.C.
Abstract:	While androgens generally have been associated with an increased cardiovascular risk, recent studies indicate potential beneficial acute effects of testosterone. However, detailed evaluation of chronic and acute actions of testosterone on the function of cardiac I(Ca,L) and intracellular Ca(2+) handling is limited. To clarify this situation we performed whole-cell and single-channel analysis of I(Ca,L), recordings of Ca(2+) sparks, measurements of contractility and quantitative real-time RT-PCR in rat cardiomyocytes following testosterone pretreatment and acute testosterone application. Pretreatment with testosterone 100nM for 24-30h increased whole-cell I(Ca,L) from 3.8+/-0.8pA/pF (n=10) to 10.1+/-0.31pA/pF (n=9) at +10mV (p<0.001). Increase of I(Ca,L) density was caused by both, increased expression levels of the alpha 1C subunit of L-type calcium channel and a pronounced increment of the single-channel activity (availability 81.8+/-3.15% versus 37.1+/-7.01%; open probability 12.8+/-3.09% versus 1.0+/-0.62%, p<0.01). Moreover, testosterone pretreatment significantly increased the frequency of Ca(2+) sparks and improved myocytes contractility without altering SR Ca(2+) load. All chronic effects could be inhibited by flutamide. In contrast acute testosterone administration significantly reduced I(Ca,L) density. Indeed, on the single-channel level acute testosterone application completely reversed the chronic testosterone-mediated effects, and antagonized the chronic testosterone effects on Ca(2+) spark frequency, which was unaffected by flutamide. Thus, testosterone pretreatment activates I(Ca,L) via nuclear receptor-mediated pathways, while testosterone acutely blocks I(Ca,L) in a direct manner. Thus, testosterone chronically affects the basal level of intracellular Ca(2+) handling, which in addition rapidly may be modulated by acute changes of hormone levels.
Keywords:	Ion channels, Hormones, Ca channel, Ca sparks, Electrophysiology, Myocytes
Source:	Cell Calcium
ISSN:	0143-4160
Publisher:	Elsevier
Volume:	41
Number:	5
Page Range:	467-477
Date:	1 May 2007
Official Publication:	https://doi.org/10.1016/j.ceca.2006.09.003
PubMed:	View item in PubMed

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