title: Myofilament Calcium Sensitivity: Role in Regulation ofIn vivoCardiac Contraction and Relaxation.
abstract: Myofilament calcium sensitivity is an often-used indicator of cardiac muscle function, often assessed in disease states such as hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). While assessment of calcium sensitivity provides important insights into the mechanical force-generating capability of a muscle at steady-state, the dynamic behavior of the muscle cannot be sufficiently assessed with a force-pCa curve alone. The equilibrium dissociation constant (Kd) of the force-pCa curve depends on the ratio of the apparent calcium association rate constant (kon) and apparent calcium dissociation rate constant (koff) of calcium on TnC and as a stand-alone parameter cannot provide an accurate description of the dynamic contraction and relaxation behavior without the additional quantification of konor koff, or actually measuring dynamic twitch kinetic parameters in an intact muscle. In this review, we examine the effect of length, frequency, and beta-adrenergic stimulation on myofilament calcium sensitivity and dynamic contraction in the myocardium, the effect of membrane permeabilization/mechanical- or chemical skinning on calcium sensitivity, and the dynamic consequences of various myofilament protein mutations with potential implications in contractile and relaxation behavior.
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Medical Scientist Training Program and Biomedical Sciences Graduate Program, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Biesiadecki
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Ziolo
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Davis
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical CenterColumbus, OH, USA; Department of Internal Medicine, The Ohio State University Wexner Medical CenterColumbus, OH, USA.
authors.forename: Paul M L
authors.initials: PM
authors.lastname: Janssen
keywords: desensitize; kinetics; muscle; sensitize; twitch