HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Tsang, S. Articles by Wong, T.-M. Search for Related Content PubMed PubMed Citation Articles by Tsang, S. Articles by Wong, T.-M.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Testosterone-augmented contractile responses to ₁- and β₁-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

¹Department of Physiology, Li Ka Shing Faculty of Medicine, and ²Hong Kong University School of Professional and Continuing Education, The University of Hong Kong, Hong Kong, China

Submitted 15 April 2008 ; accepted in final form 14 December 2008

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both ₁- and β₁-adrenoceptors by increasing Ca²⁺ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca²⁺ from cytosol via Ca²⁺-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 µg/100 g body wt) in the presence of norepinephrine (10^–7 M), the ₁-adrenoceptor agonist phenylephrine (10^–6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10^–7 M) in the presence of 5 x 10^–7 M ICI-118,551, a β₂-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca²⁺ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca²⁺ release via the ryanodine receptor (RyR) or releasable Ca²⁺ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured ⁴⁵Ca²⁺ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca²⁺ reuptake by sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) and removal via the sarcolemmal Na⁺/Ca²⁺ exchanger (NCX). We correlated Ca²⁺ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of ₁- and β₁-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca²⁺ release via the RyR and faster Ca²⁺ removal out of the cytosol via SERCA and NCX.

orchiectomy; androgen receptor; left ventricular developed pressure; velocity of contraction and relaxation; electrical-induced intracellular Ca²⁺ concentration transients; caffeine-induced intracellular Ca²⁺ concentration transients; ryanodine receptor; sarco(endo)plasmic reticulum Ca²⁺-ATPase; Na⁺/Ca²⁺ exchanger