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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sipido, K. R. Search for Related Content PubMed PubMed Citation Articles by Sipido, K. R. Related Collections Calcium cycling/excitation-contraction coupling Heart failure - basic studies Ion channels/membrane transport

(Circulation Research. 2000;87:966.)
© 2000 American Heart Association, Inc.

Editorial

Local Ca²⁺ Release in Heart Failure

Timing Is Important

Karin R. Sipido

From the Laboratory of Experimental Cardiology, University of Leuven, Belgium.

Correspondence to Karin R. Sipido, MD, PhD, Laboratory of Experimental Cardiology, KUL, Campus Gasthuisberg O/N 7th floor, Herestraat 49, B-3000 Leuven, Belgium. E-mail Karin.Sipido@med.kuleuven.ac.be

Key Words: myocyte • heart failure • sparks

	Introduction

 
For many years, the treatment of heart failure has focused, successfully, on the neurohumoral pathways, but recently more attention has again been given to the heart itself and ways to improve the phenotype of the failing cardiomyocyte. [Ca²⁺]_i transients from myocytes of failing human hearts typically have a low amplitude and slow decline at normal frequencies.^{1 2 3} The slower decline has been attributed to a decreased Ca²⁺ uptake into the sarcoplasmic reticulum (SR), as evidenced by decreased expression levels of the SR Ca²⁺-ATPase, SERCA, at both the mRNA and protein levels.⁴ Such deficiency of SERCA will lead to a decrease in SR content.⁵ Consequently, much attention has been dedicated to the potential treatment of heart failure by improving SERCA function either by pharmacological block of the inhibitory protein phospholamban (PLB)⁶ or by gene therapy targeted at SERCA itself or PLB. Such strategies have been successful in improving function in animal models^{7 8} and in isolated human myocytes.⁹ Although this seems a promising therapeutic venue, it should not mislead us into thinking that SERCA deficiency is the major (or even the only) defect responsible for the failing phenotype.⁸ In the last years, a number of other mechanisms have been identified that may contribute to the phenotype of human end-stage heart failure and may be targets for therapy. Upregulation of the Na⁺-Ca²⁺ exchange has been proposed as a compensatory mechanism for the decrease in SERCA function and could improve relaxation.¹⁰ However, upregulation of Na⁺-Ca²⁺ exchange may have negative consequences as . . . [Full Text of this Article]

This article has been cited by other articles:

				L.-S. Song, Y. Pi, S.-J. Kim, A. Yatani, S. Guatimosim, R. K. Kudej, Q. Zhang, H. Cheng, L. Hittinger, B. Ghaleh, et al. Paradoxical Cellular Ca2+ Signaling in Severe but Compensated Canine Left Ventricular Hypertrophy Circ. Res., September 2, 2005; 97(5): 457 - 464. [Abstract] [Full Text] [PDF]

				M. Inoue and J. H.B. Bridge Ca2+ Sparks in Rabbit Ventricular Myocytes Evoked by Action Potentials: Involvement of Clusters of L-Type Ca2+ Channels Circ. Res., March 21, 2003; 92(5): 532 - 538. [Abstract] [Full Text] [PDF]

				J. Fauconnier, S. Bedut, J.-Y. Le Guennec, D. Babuty, and S. Richard Ca2+ current-mediated regulation of action potential by pacing rate in rat ventricular myocytes Cardiovasc Res, March 1, 2003; 57(3): 670 - 680. [Abstract] [Full Text] [PDF]

				D. T. Lucas, P. Aryal, L. I. Szweda, W. J. Koch, and L. A. Leinwand Alterations in mitochondrial function in a mouse model of hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H575 - H583. [Abstract] [Full Text] [PDF]