Faculty Collaboration Database

Sex differences in expression of calcium-handling proteins and beta-adrenergic receptors in rat heart ventricle. Life Sci 2005 Apr 22;76(23):2735-49

Date

03/29/2005

Pubmed ID

15792839

DOI

10.1016/j.lfs.2004.12.013

Scopus ID

2-s2.0-15544371593 (requires institutional sign-in at Scopus site)   87 Citations

Abstract

Human studies reveal sex differences in myocardial function as well as in the incidence and manifestation of heart disease. Myocellular Ca(2+) cycling regulates normal contractile function; whereas cardiac dysfunction in heart failure has been associated with alterations in Ca(2+)-handling proteins. Beta-adrenergic receptor (beta-AR) signaling regulates activity of several Ca(2+)-handling proteins and alterations in beta-AR signaling are associated with heart disease. This study examines sex differences in expression of beta(1)-AR, beta(2)-AR, and Ca(2+)-handling proteins including: L-type calcium channel (Ca(v)1.2) , ryanodine calcium-release channels (RyR), sarcoplasmic reticular Ca(2+) ATPase (SERCA2), phospholamban (PLB) and Na(+)-Ca(2+) exchange protein (NCX) in healthy hearts from male and female Sprague-Dawley rats. Protein levels were examined using Western blot analysis. Abundance of mRNA was determined by real time RT-PCR normalized to abundance of GAPDH mRNA. Contraction parameters were measured in right ventricular papillary muscle in the presence and absence of isoproterenol. Results demonstrate that female ventricle has significantly higher levels of Ca(v)1.2, RyR, and NCX protein compared to males. Messenger RNA abundance for RyR, and NCX protein was significantly higher in females whereas Ca(v)1.2 mRNA was higher in males. No differences were detected in beta-ARs, SERCA2 or PLB. Female right papillary muscle had a faster maximal rate of force development and decline (+/- dF/dt). There were no sex differences in response to isoproterenol. Results show significant sex differences in expression of key ventricular Ca(2+)-handling proteins that are associated with small functional differences in +/- dF/dt. Further studies will determine whether differences in the abundance of these key proteins play a role in sex disparities in the incidence and manifestation of heart disease.

Author List

Chu SH, Sutherland K, Beck J, Kowalski J, Goldspink P, Schwertz D

MESH terms used to index this publication - Major topics in bold

Animals
Biomarkers
Blotting, Western
Calcium Channels, L-Type
Calcium-Binding Proteins
Calcium-Transporting ATPases
Female
Heart Ventricles
Male
Muscle Contraction
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta-2
Receptors, Adrenergic, beta-3
Reverse Transcriptase Polymerase Chain Reaction
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Sex Factors
Sodium-Calcium Exchanger