Phospholemman deficiency in postinfarct hearts: enhanced contractility but increased mortality

Area of Science:

• Cardiovascular Physiology
• Molecular Cardiology
• Cardiac Metabolism

Background:

• Phospholemman (PLM) regulates intracellular sodium ([Na(+) ](i)) and calcium ([Ca(2+)](i)) by interacting with Na(+)-K(+)-ATPase (NKA) and Na(+)/Ca(2+) exchanger (NCX1).
• PLM expression and phosphorylation are altered following myocardial infarction (MI) and in heart failure.

Purpose of the Study:

• To investigate the detrimental effects of absent PLM regulation on NKA and NCX1 in a mouse model of MI.
• To determine if genetic absence of PLM impacts cardiac function and survival post-MI.

Main Methods:

• Utilized PLM-knockout (KO) and wild-type (WT) mice subjected to MI.
• Assessed cardiac hypertrophy, left ventricular ejection fraction, myocyte calcium transients, and NCX1 currents.
• Monitored survival rates post-MI.

Main Results:

• PLM-KO-MI hearts showed less depressed ejection fraction compared to WT-MI hearts, despite similar infarct sizes.
• Genetic absence of PLM ameliorated abnormal myocyte calcium handling and contraction in post-MI hearts.
• While cardiac performance improved in PLM-KO mice, their survival rate was reduced after MI.

Conclusions:

• Alterations in PLM expression and phosphorylation are critical adaptive responses to MI.
• Complete absence of PLM regulation of NKA and NCX1 is detrimental to survival in post-MI animals.
• PLM plays a vital, albeit complex, role in cardiac adaptation and survival following ischemic injury.