Passive Properties of Single Skeletal Muscle Fibers are Altered in Heart Failure Patients

Abstract

We previously demonstrated that myosin heavy chain (MHC) content is decreased in skeletal muscle fibers from heart failure patients, thereby altering Ca2+-activated (pCa 4.5) contractile properties. In this study, we examined chemically-skinned, single human skeletal muscle fibers under relaxed conditions (low [Ca2+], pCa 8) using small amplitude sinusoidal analysis to determine whether the loss of MHC content affects their viscoelastic properties. We obtained vastus lateralis (quadriceps) muscle from needle biopsies of 9 patients and 5 sedentary controls. Surprisingly, Type I (slow twitch) and Type IIA (fast twitch) fibers produced slight but significant positive oscillatory work under relaxed conditions at 25°C, indicating the presence of cross-bridge cycling. This positive oscillatory work persisted when [Ca2+]levels were lowered even further (to pCa 9). Addition of 40 mM 2,3-butanedione monoxime (BDM) or 100 μM blebbistatin, inhibitors of skeletal muscle myosin ATPase, to a subset of Type I and IIA fibers eliminated their positive work output and reduced their high frequency elastic and viscous moduli. Type I fibers from heart failure patients had lower isometric tensions as well as lower elastic and viscous moduli compared to controls; whereas, Type IIA fibers from patients had tension values similar to controls, while the frequency of maximum work output (an indicator of myosin kinetics) was greater. Taken together, these results demonstrate that cross-bridges contribute to the viscoelastic properties of human skeletal muscle in the ‘relaxed’ state (low intracellular [Ca2+]) and that cycling myosin heads may contribute to resting muscle tone. As under Ca2+-activated conditions, heart failure affects relaxed muscle properties differentially depending upon fiber type. Decreased resting muscle tone in heart failure patients may decrease postural stability and contribute to a reduced ability to perform activities of daily living.