Calcium cycling proteins and their association with heart failure

Abstract

Heart failure (HF) has reached epidemic proportions in the United States and is one of the most important challenges to public health. Severe congestive HF is associated with substantial morbidity and mortality. HF afflicts approximately 5 million patients and contributes to 3 million hospitalizations and 300,000 deaths yearly. Late-stage HF has a poor prognosis, and therapeutic options are limited. Defective excitation–contraction (EC) coupling in HF may result from altered density or function of proteins relevant for Ca2+ homeostasis.

Figure 1

Excitation-contraction signaling in cardiomyocytes. Ca²⁺ influx through L-type Ca²⁺ channels. AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; Gi, inhibitory G protein; Gs; stimulatory G protein; I-1, protein phosphatase inhibitor-1; NCX, sodium–calcium exchanger; PKA, protein kinase A; PLB, phospholamban; PP1, protein phosphatase 1; RyR, ryanodine receptor; SERCA2a, sarco/endoplasmic reticulum Ca²⁺-ATPase 2a; β-AR, β-adrenergic receptor.