Stretch modulation of cardiac contractility: importance of myocyte calcium during the slow force response
- 17 Downloads
The mechanical response of the heart to myocardial stretch has been understood since the work of muscle physiologists more than 100 years ago, whereby an increase in ventricular chamber filling during diastole increases the subsequent force of contraction. The stretch-induced increase in contraction is biphasic. There is an abrupt increase in the force that coincides with the stretch (the rapid response), which is then followed by a slower response that develops over several minutes (the slow force response, or SFR). The SFR is associated with a progressive increase in the magnitude of the Ca2+ transient, the event that initiates myocyte cross-bridge cycling and force development. However, the mechanisms underlying the stretch-dependent increase in the Ca2+ transient are still debated. This review outlines recent literature on the SFR and summarizes the different stretch-activated Ca2+ entry pathways. The SFR might result from a combination of several different cellular mechanisms initiated in response to activation of different cellular stretch sensors.
KeywordsCardiac stretch Calcium influx Slow force response Stretch-activated channels Autocrine/paracrine response G-coupled protein receptors
We acknowledge funding from the University of Auckland Faculty Research and Development Fund and the Auckland Medical Research Foundation.
Compliance with ethical standards
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Human and animal rights and informed consent
This article does not contain any studies with human participants performed by any of the authors.
- Alvarez BV, Perez NG, Ennis IL, Camilion de Hurtado MC, Cingolani HE (1999) Mechanisms underlying the increase in force and Ca(2+) transient that follow stretch of cardiac muscle: a possible explanation of the Anrep effect. Circ Res 85:716–722. https://doi.org/10.1161/01.res.85.8.716 CrossRefPubMedGoogle Scholar
- Bers DM (2008) Calcium cycling and signaling in cardiac myocytes. Annu Rev Physiol 70:23–49. https://doi.org/10.1146/annurev.physiol.70.113006.100455 CrossRefPubMedGoogle Scholar
- Frank O (1895) Zur Dynamik des Herzmuskels : Habilitationsschrift zur Erlangung der Venia Legendi der Medizinischen Fakultät der Ludwig-Mazimilians-Universität zu München. Druck von R, OldenbourgGoogle Scholar
- Luers C, Fialka F, Elgner A, Zhu D, Kockskamper J, von Lewinski D, Pieske B (2005) Stretch-dependent modulation of [Na+]i, [Ca2+]i, and pHi in rabbit myocardium--a mechanism for the slow force response. Cardiovasc Res 68:454–463. https://doi.org/10.1016/j.cardiores.2005.07.001 CrossRefPubMedGoogle Scholar
- Ohtsu H, Suzuki H, Nakashima H, Dhobale S, Frank GD, Motley ED, Eguchi S (2006) Angiotensin II signal transduction through small GTP-binding proteins: mechanism and significance in vascular smooth muscle cells. Hypertension 48:534–540. https://doi.org/10.1161/01.HYP.0000237975.90870.eb CrossRefPubMedGoogle Scholar
- von Lewinski D, Stumme B, Fialka F, Luers C, Pieske B (2004) Functional relevance of the stretch-dependent slow force response in failing human myocardium. Circ Res 94:1392–1398. https://doi.org/10.1161/01.RES.0000129181.48395.ff CrossRefGoogle Scholar
- Ward ML, Shen X, Greenwood DR (2014) Use of liquid chromatography-mass spectrometry (LC-MS) to detect substances of nanomolar concentration in the coronary effluent of isolated perfused hearts. Prog Biophys Mol Biol 115:270–278. https://doi.org/10.1016/j.pbiomolbio.2014.07.005 CrossRefPubMedGoogle Scholar