The Control of Diastolic Calcium in the Heart: Basic Mechanisms and Functional Implications

Normal cardiac function requires that intracellular Ca²⁺ concentration be reduced to low levels in diastole so that the ventricle can relax and refill with blood. Heart failure is often associated with impaired cardiac relaxation. Little, however, is known about how diastolic intracellular Ca²⁺ concentration is regulated. This article first discusses the reasons for this ignorance before reviewing the basic mechanisms that control diastolic intracellular Ca²⁺ concentration. It then considers how the control of systolic and diastolic intracellular Ca²⁺ concentration is intimately connected. Finally, it discusses the changes that occur in heart failure and how these may result in heart failure with preserved versus reduced ejection fraction.