Phospholamban ablation enhances relaxation in the murine soleus.
Phospholamban (PLB) is expressed in slow-twitch skeletal, cardiac, and smooth muscles. Several studies have indicated that it is an important regulator of basal contractility and the stimulatory responses to isoproterenol in the mammalian heart. To determine whether PLB is also a key modulator of slow-twitch skeletal muscle contractility, we examined isometric twitch contractions of isolated, intact soleus muscles from wild-type (WT) and PLB-deficient mice in parallel. Soleus muscles from PLB-deficient mice exhibited a significant (25%) decrease in the time to half relaxation, with no change in contraction time compared with WT soleus muscles. The observed enhancement of relaxation in the PLB-deficient soleus was not associated with alterations in the protein levels of either the sarcoplasmic reticular Ca(2+)-adenosinetriphosphatase or the ryanodine receptor. Examination of the effects of isoproterenol on the twitch kinetics of these muscles revealed 1) no effect on the contraction times of either WT or PLB-deficient muscles and 2) a significant decrease in the half relaxation time of the WT soleus, whereas this parameter remained unchanged in the PLB-deficient muscle. Furthermore, with maximal isoproterenol stimulation, the half relaxation time of the WT soleus was similar to that of the nonstimulated PLB-deficient soleus. These results suggest that PLB is a key determinant of relaxation in slow-twitch skeletal muscle under basal conditions and during isoproterenol stimulation.
Slack
J P
JP
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575, USA.
Grupp
I L
IL
Luo
W
W
Kranias
E G
EG
D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002678:Chimera; D005260:Female; D006579:Heterozygote; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D009124:Muscle Proteins; D012433:Ryanodine; D019837:Ryanodine Receptor Calcium Release Channel; D000099211:Phospholamban