title: Calcium in the heart: from physiology to disease.
abstract: Contraction of the heart results from an increase of cytoplasmic Ca(2+) concentration ([Ca(2+)]i), the so-called systolic Ca(2+) transient. Most of this results from the release of Ca(2+) from the sarcoplasmic reticulum (SR) through the ryanodine receptor (RyR). In turn, the amplitude of this Ca(2+) transient determines the contractility of the heart. In this lecture, I consider the factors which govern the size and stability of this Ca(2+) release. The amplitude of the Ca(2+) transient is a steep function of SR Ca, resulting in a requirement for very precise beat-to-beat regulation of SR Ca content. This is achieved by a simple negative feedback mechanism, in which an increase of SR Ca content increases the size of the Ca(2+) transient, resulting in a decrease of Ca(2+) influx on the L-type Ca(2+) current and an increase of efflux through Na(+)-Ca(2+) exchange. Changing the activity of any of the Ca(2+)-cycling proteins will change the steady-state SR Ca content. This feedback mechanism has many consequences, including the fact that a change of RyR open probability has a only a temporary effect on the amplitude of the Ca(2+) transient due to a compensating change of SR Ca content. The remainder of the article considers the link between intracellular Ca(2+) waves and arrhythmias. This is done in the context of catecholaminergic polymorphic ventricular tachycardia, which is an inherited arrhythmia syndrome, in many cases due to a RyR mutation, where arrhythmias occur during exercise as a result of β-adrenergic stimulation. Calcium waves occur only when the SR Ca content exceeds a threshold level. Our data show that the threshold is reduced by the RyR mutation and that the adrenergic stimulation increases SR Ca content.
authors.affiliation: Unit of Cardiac Physiology, University of Manchester, Manchester, UK eisner@man.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Eisner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000378:metabolism*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D002118:Calcium