Figure 5.

Effects of inhibition of Na⁺/Ca²⁺ exchanger by phosphorylated phospholemman on β‐adrenergic response in vivo. Left ventricles of phospholemman‐null (KO) mice are injected with recombinant adeno‐associated virus, serotype 9, expressing either green fluorescent protein (GFP) (€; n= 5) or the phosphomimetic phospholemman S68E mutant (•; n= 7). S68E mutant inhibits Na⁺/Ca²⁺ exchanger but has no effect on Na⁺‐K⁺‐ATPase. ¹² , ³¹ , ⁵⁷ Five weeks after virus injection, in vivo hemodynamics (+dP/dt) are measured in anesthetized mice. ³² Note that with increasing doses of isoproterenol, KO‐S68E hearts contract significantly better than KO‐GFP hearts. Since isoproterenol has no effect on Na⁺‐K⁺‐ATPase in phospholemman‐null myocytes, ²⁵ , ³² [Na⁺]_i is similar between KO‐S68E and KO‐GFP hearts (data not shown). Enhanced contractility in KO‐S68E hearts is therefore due to inhibition of Na⁺/Ca²⁺ exchanger by the S68E mutant.