Role of oxidants on calcium and sodium movement in healthy and diseased cardiac myocytes

Abstract

In this review article we give an overview of current knowledge with respect to redox-sensitive alterations in Na(+) and Ca(2+) handling in the heart. In particular, we focus on redox-activated protein kinases including cAMP-dependent protein kinase A (PKA), protein kinase C (PKC), and Ca/calmodulin-dependent protein kinase II (CaMKII), as well as on redox-regulated downstream targets such as Na(+) and Ca(2+) transporters and channels. We highlight the pathological and physiological relevance of reactive oxygen species and some of its sources (such as NADPH oxidases, NOXes) for excitation-contraction coupling (ECC). A short outlook with respect to the clinical relevance of redox-dependent Na(+) and Ca(2+) imbalance will be given.

Keywords: (late), late Na(+) current; A-kinase anchor protein; AKAP; AP; APD; Ang II; BH4; Ca handling; Ca/calmodulin-dependent protein kinase II; CaM; CaMKII; CaMKIIδ(C); Calcium; Coupling; DAD; DAG; DCM; DOX; EAD; ECC; ER; ETC; Exciation—contraction; FKBP12.6; GSH; HF; HFpEF; HFrEF; I(Ca); I(Na); I(Ti); I(to); L-type Ca(2+) channels; LTCC; Late Na current; MPT; NADH; NADPH; NADPH oxidase; NCX1; NHE; NKA; NO; NOS; NOS1; NOS2; NOS3; NOX; Na(+) channel protein; Na(+)/H(+) exchanger; NaV1.5; ONOO(-); PKA; PKC; PLB; PLM; PPI-1; ROS; RyR2; SERCA2a; SOD; SR; SR Ca leak; Sodium; Trx; XOR; action potential; action potential duration; angiotensin II; cAMP; cAMP-dependent protein kinase A; calmodulin; calstabin; cyclic adenosine monophosphate; cytosolic splice variant of Ca/calmodulin-dependent protein kinase II; delayed afterdepolarization; diacylglycerol; dilated cardiomyopathy; doxorubicin; early afterdepolarizations; electron transport chain in the mitochondria; endoplasmic reticulum; endothelial nitric oxide synthase (also eNOS); excitation-contraction coupling; gluthathione; heart failure; heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; inducible nitric oxide synthase (also iNOS); inward Ca(2+) current; inward Na(+) current; mitochondrial permeability transition; neuronal nitric oxide synthase (also nNOS); nicotinamide adenine dinucleotide; nicotinamide adenine dinucleotide phosphate; nitric oxide; nitric oxide synthase; outward rectifying K(+) currents; peroxynitrite; phospholamban; phospholemman; protein kinase C; protein phosphatase inhibitor 1; reactive oxygen species; ryanodine receptors; sarcolemmal Na(+)/Ca(2+) exchanger; sarcolemmal Na(+)/K(+) ATPase; sarcoplasmic reticulum; sarcoplasmic reticulum Ca(2+)-ATPase; superoxide dismutase; tetrahydrobiopterin; thioredoxin; transient inward current; xanthine oxidase.