Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1α2 Mouse Model of High Affinity for Cardiotonic Steroids.

The Na/K-ATPase is the specific receptor for cardiotonic steroids (CTS) such as ouabain and digoxin. At pharmacological concentrations used in the treatment of cardiac conditions, CTS inhibit the ion-pumping function of Na/K-ATPase. At much lower concentrations, in the range of those reported for endogenous CTS in the blood, they stimulate hypertrophic growth of cultured cardiac myocytes through initiation of a Na/K-ATPase-mediated and reactive oxygen species (ROS)-dependent signaling.

KLF2 in Myeloid Lineage Cells Regulates the Innate Immune Response during Skeletal Muscle Injury and Regeneration.

Skeletal muscle repair and regeneration after injury requires coordinated interactions between the innate immune system and the injured muscle. Myeloid cells predominate in these interactions. This study examined the role of KLF2, a zinc-finger transcription factor that regulates immune cell activation, in specifying myeloid cell functions during muscle regeneration.

K⁺ and Rb⁺ Affinities of the Na,K-ATPase α₁ and α₂ Isozymes: An Application of ICP-MS for Quantification of Na⁺ Pump Kinetics in Myofibers.

The potassium affinities of Na,K-ATPase isozymes are important determinants of their physiological roles in skeletal muscle. This study measured the apparent K⁺ and Rb⁺ affinities of the Na,K-ATPase α₁ and α₂ isozymes in intact, dissociated myofibers obtained from WT and genetically altered mice (α₁α₂ and skα₂). It also validates a new method to quantify cations in intact, dissociated myofibers, using inductively coupled plasma mass spectrometry (ICP-MS).

Isoform-specific role of Na/K-ATPase α1 in skeletal muscle.

The distribution of Na/K-ATPase α-isoforms in skeletal muscle is unique, with α1 as the minor (15%) isoform and α2 comprising the bulk of the Na/K-ATPase pool. The acute and isoform-specific role of α2 in muscle performance and resistance to fatigue is well known, but the isoform-specific role of α1 has not been as thoroughly investigated. In vitro, we reported that α1 has a role in promoting cell growth that is not supported by α2.

Pivotal role of α2 Na pumps and their high affinity ouabain binding site in cardiovascular health and disease.

Reduced smooth muscle (SM)-specific α2 Na pump expression elevates basal blood pressure (BP) and increases BP sensitivity to angiotensin II (Ang II) and dietary NaCl, whilst SM-α2 overexpression lowers basal BP and decreases Ang II/salt sensitivity. Prolonged ouabain infusion induces hypertension in rodents, and ouabain-resistant mutation of the α2 ouabain binding site (α2 mice) confers resistance to several forms of hypertension. Pressure overload-induced heart hypertrophy and failure are attenuated in cardio-specific α2 knockout, cardio-specific α2 overexpression and α2 mice.