Impaired muscle Ca²⁺ and K⁺ regulation contribute to poor exercise performance post-lung transplantation

Lung transplant recipients (LTx) exhibit marked peripheral limitations to exercise. We investigated whether skeletal muscle Ca²⁺ and K ⁺ regulation might be abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and arterialized venous plasma [K ⁺] (where brackets denote concentration) were measured during incremental exercise. Vastus lateralis muscle was biopsied at rest and analyzed for sarcoplasmic reticulum Ca²⁺ release, Ca²⁺ uptake, and Ca²⁺-ATPase activity rates; fiber composition; Na⁺-K ⁺-ATPase (K⁺-stimulated 3-O-methylfluorescein phosphatase) activity and content ([³H]ouabain binding sites); as well as for [H⁺] and H⁺-buffering capacity. Peak oxygen consumption was 47% less in LTx (P < 0.05). LTx had lower Ca²⁺ release (34%), Ca²⁺ uptake (31%), and Ca²⁺-ATPase activity (25%) than controls (P < 0.05), despite their higher type II fiber proportion (LTx, 75. 0 ± 5.8%; controls, 43.5 ± 2.1%). Muscle [H⁺] was elevated in LTx (P < 0.01), but buffering capacity was similar to controls. Muscle 3-O-methylfluorescein phosphatase activity was 31% higher in LTx (P < 0.05), but [³H]ouabain binding content did not differ significantly. However, during exercise, the rise in plasma [K⁺]-to-work ratio was 2.6-fold greater in LTx (P < 0.05), indicating impaired K⁺ regulation. Thus grossly subnormal muscle calcium regulation, with impaired potassium regulation, may contribute to poor muscular performance in LTx.