eNOS and nNOS in cardiac excitation–contraction coupling. In cardiac myocytes, eNOS associates with caveolin-3 at the sarcolemma, where it blunts inotropic response to isoproterenol stimulation. nNOS associates with the ryanodine receptor at the sarcoplasmic reticulum and is required for proper Ca2+-mediated Ca2+ release. Arrow thickness reflects magnitude of Ca2+ flux. Cav3, caveolin-3; β-AR, β-adrenergic receptor; RyR, ryanodine receptor; FKBP, FK506-binding protein; PLB, phospholamban; SERCA, sarcoplasmic reticulum Ca2+-ATPase.