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) All Versions of this Article: 293/1/R30    most recent 00508.2006v1 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 HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Hiranandani, N. Articles by Janssen, P. M. L. Search for Related Content PubMed PubMed Citation Articles by Hiranandani, N. Articles by Janssen, P. M. L.

CALL FOR PAPERS
Regulation of Cardiac Muscle Contraction

Frequency-dependent contractile strength in mice over- and underexpressing the sarco(endo)plasmic reticulum calcium-ATPase

Department of Physiology and Cell Biology, The Ohio State University, Columbus, Ohio

Submitted 18 July 2006 ; accepted in final form 18 January 2007

One of the prominent markers of end-stage heart failure at the molecular level is a decrease in function and/or expression of the sarcoplasmic reticulum ATPase protein [sarco(endo)plasmic reticulum calcium-ATPase, SERCA]. It has been often postulated that a decrease in SERCA pump activity can contribute in a major way to decreased cardiac function. To establish a functional relationship, we assessed how alterations in SERCA activity level affect basic contractile function in healthy myocardium devoid of other significant molecular changes. We investigated baseline contractile function, frequency-dependent activation, and -adrenergic response in ultrathin trabeculae isolated from hearts of mice overexpressing SERCA (transgenic, TG), underexpressing SERCA2a (heterozygous knockout, Het), and their respective wild-type (WT) littermates. At physiological temperature and frequency, compared with their respective WT littermates, SERCA1a mice displayed increased developed force at frequencies of 4–8 Hz (90% increase at 4 Hz) and force equal to WT mice at 10–14 Hz. Force development at 4 Hz in presence of 1 µM isoproterenol was similar in TG and WT mice. In Het mice, developed force was nearly identical at the lower end of the frequency range (4–8 Hz) but slightly depressed at higher frequency (P < 0.05 at 14 Hz). In presence of 1 µM isoproterenol, developed force at 4 Hz was equal to that in WT mice. Compared with normal levels, increased SERCA activity enhanced force development only at subphysiological frequencies. A reduction in SERCA activity only showed a depression of force at the higher frequency range. Thus generalizations regarding the correlation between SERCA activity and contractility can be highly ambiguous, because this relationship is critically dependent on other factors including stimulation frequency.

trabeculae; mouse; -adrenergic stimulation; force-frequency response

This article has been cited by other articles:

				J. M. O'Donnell, A. Fields, X. Xu, S. A. K. Chowdhury, D. L. Geenen, and J. Bi Limited functional and metabolic improvements in hypertrophic and healthy rat heart overexpressing the skeletal muscle isoform of SERCA1 by adenoviral gene transfer in vivo Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2483 - H2494. [Abstract] [Full Text] [PDF]

				K. S. McDonald Regulation of cardiac muscle contraction: how paramount are the sarcomeres? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R961 - R962. [Full Text] [PDF]