scholarly journals Myosin Phosphatase Isoforms as Determinants of Smooth Muscle Contractile Function and Calcium Sensitivity of Force Production

2014 ◽  
Vol 21 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Rachael P. Dippold ◽  
Steven A. Fisher
Keyword(s):  
Smooth Muscle ◽  
Contractile Function ◽  
Force Production ◽  
Calcium Sensitivity ◽  
Myosin Phosphatase ◽  
Muscle Contractile

Dynamic changes in expression of myosin phosphatase in a model of portal hypertension

2004 ◽  
Vol 286 (5) ◽  
pp. H1801-H1810 ◽  
Author(s):  
Michael C. Payne ◽  
Hai-Ying Zhang ◽  
Yuichi Shirasawa ◽  
Yasuhiko Koga ◽  
Mitsuo Ikebe ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Portal Hypertension ◽  
Leucine Zipper ◽  
Splice Variants ◽  
Phenotypic Diversity ◽  
Vena Cava ◽  
Force Production ◽  
Calcium Sensitivity ◽  
Myosin Phosphatase ◽  
Minor Variation

Myosin phosphatase is a target for signaling pathways that modulate calcium sensitivity of force production in smooth muscle. Myosin phosphatase targeting subunit 1 (MYPT1) isoforms are generated by cassette-type alternative splicing of exons in the central and 3′ portion of the transcript. Exclusion of the 3′ alternative exon, coding for the leucine zipper (LZ)-positive MYPT1 isoform, is associated with the ability to desensitize to calcium (relax) in response to NO/cGMP-dependent signaling. We examined expression of MYPT1 isoforms and smooth muscle phenotype in normal rat vessels and in a prehepatic model of portal hypertension characterized by arteriolar dilation. The large capacitance vessels, aorta, pulmonary artery, and inferior vena cava expressed predominantly the 3′ exon-out/LZ-positive MYPT1 isoform. The first-order mesenteric resistance artery (MA1) and portal vein (PV) expressed severalfold higher levels of MYPT1 with predominance of the 3′ exon-included/LZ-negative isoform. There was minor variation in the presence of the MYPT1 central alternative exons. Myosin heavy and light chain splice variants in part cosegregated with MYPT1 isoforms. In response to portal hypertension induced by PV ligature, abundance of MYPT1 in PV and MA1 was significantly reduced and switched to the LZ-positive isoform. These changes were evident within 1 day of PV ligature and were maintained for up to 10 days before reverting to control values at day 14. Alteration of MYPT1 expression was part of a complex change in protein expression that can be generalized as a modulation from a phasic (fast) to a tonic (slow) contractile phenotype. Implications of vascular smooth muscle phenotypic diversity and reversible phenotypic modulation in portal hypertension with regards to regulation of blood flow are discussed.

Selected Contribution: Mechanical strain increases force production and calcium sensitivity in cultured airway smooth muscle cells

2000 ◽  
Vol 89 (5) ◽  
pp. 2092-2098 ◽  
Author(s):  
Paul G. Smith ◽  
Chaity Roy ◽  
Steven Fisher ◽  
Qi-Quan Huang ◽  
Frank Brozovich
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Force Production ◽  
Muscle Cells ◽  
Calcium Sensitivity ◽  
Airway Smooth Muscle Cells ◽  
Maximal Force

Cultured airway smooth muscle cells subjected to cyclic deformational strain have increased cell content of myosin light chain kinase (MLCK) and myosin and increased formation of actin filaments. To determine how these changes may increase cell contractility, we measured isometric force production with changes in cytosolic calcium in individual permeabilized cells. The pCa for 50% maximal force production was 6.6 ± 0.4 in the strain cells compared with 5.9 ± 0.3 in control cells, signifying increased calcium sensitivity in strain cells. Maximal force production was also greater in strain cells (8.6 ± 2.9 vs. 5.7 ± 3.1 μN). The increased maximal force production in strain cells persisted after irreversible thiophosphorylation of myosin light chain, signifying that increased force could not be explained by differences in myosin light chain phosphorylation. Cells strained for brief periods sufficient to increase cytoskeletal organization but insufficient to increase contractile protein content also produced more force, suggesting that strain-induced cytoskeletal reorganization also increases force production.

Vascular Smooth Muscle Contractile Function Is Impaired during Early and Late Stages of Sepsis

1994 ◽  
Vol 56 (6) ◽  
pp. 556-561 ◽  
Author(s):  
Samuel H. Wurster ◽  
Ping Wang ◽  
Richard E. Dean ◽  
Irshad H. Chaudry
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Contractile Function ◽  
Late Stages ◽  
Muscle Contractile

scholarly journals Phosphorylation of a twitchin-related protein controls catch and calcium sensitivity of force production in invertebrate smooth muscle

1998 ◽  
Vol 95 (9) ◽  
pp. 5383-5388 ◽  
Author(s):  
M. J. Siegman ◽  
D. Funabara ◽  
S. Kinoshita ◽  
S. Watabe ◽  
D. J. Hartshorne ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Force Production ◽  
Calcium Sensitivity ◽  
Related Protein

scholarly journals Vascular Smooth Muscle Contractile Function Declines With Age in Skeletal Muscle Feed Arteries

2018 ◽  
Vol 9 ◽  
Author(s):  
John W. Seawright ◽  
Harini Sreenivasappa ◽  
Holly C. Gibbs ◽  
Samuel Padgham ◽  
Song Y. Shin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Contractile Function ◽  
Feed Arteries ◽  
Muscle Contractile ◽  
Skeletal Muscle Feed Arteries

scholarly journals Transverse tubule remodeling enhances Orai1-dependent Ca2+ entry in skeletal muscle

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Antonio Michelucci ◽  
Simona Boncompagni ◽  
Laura Pietrangelo ◽  
Maricela García-Castañeda ◽  
Takahiro Takano ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Acute Exercise ◽  
Muscle Force ◽  
Contractile Function ◽  
Force Production ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Muscle Force Production ◽  
Muscle Contractile

Exercise promotes the formation of intracellular junctions in skeletal muscle between stacks of sarcoplasmic reticulum (SR) cisternae and extensions of transverse-tubules (TT) that increase co-localization of proteins required for store-operated Ca2+ entry (SOCE). Here, we report that SOCE, peak Ca2+ transient amplitude and muscle force production during repetitive stimulation are increased after exercise in parallel with the time course of TT association with SR-stacks. Unexpectedly, exercise also activated constitutive Ca2+ entry coincident with a modest decrease in total releasable Ca2+ store content. Importantly, this decrease in releasable Ca2+ store content observed after exercise was reversed by repetitive high-frequency stimulation, consistent with enhanced SOCE. The functional benefits of exercise on SOCE, constitutive Ca2+ entry and muscle force production were lost in mice with muscle-specific loss of Orai1 function. These results indicate that TT association with SR-stacks enhances Orai1-dependent SOCE to optimize Ca2+ dynamics and muscle contractile function during acute exercise.

Abstract 1065: Class-II Histone Deacetylases Regulate Myofilament Calcium Sensitivity in the Mouse Heart

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Stephen H Smith ◽  
Mahesh P Gupta ◽  
Sadhana Samant ◽  
Madhu Gupta ◽  
Sanjeev G Shroff
Keyword(s):  
Contractile Function ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Force Production ◽  
Calcium Sensitivity ◽  
Class Ii ◽  
Skinned Fibers ◽  
Mouse Heart ◽  
Acetyl Coa ◽  
Myofilament Calcium Sensitivity

The role of phosphorylation of myofilaments in regulating cardiac muscle calcium sensitivity and force production is well established. Recently it was shown that trichostatin A (TSA), a class-I and II histone deacetylase (HDAC) inhibitor, improved cardiac contractile function in vivo . Because class-II HDACs are able to translocate to the cytoplasm from the nucleus, it is postulated that some HDACs may interact with contractile proteins and thereby regulate myofilament calcium sensitivity and/or force production. Papillary muscle strips from mouse hearts were skinned for 4 hours and then treated overnight with two structurally dissimilar HDAC inhibitors, TSA and MS275. Both HDAC inhibitors significantly increased myofilament calcium sensitivity as quantified by pCa 50 [Baseline (n=9): 5.75±0.04; TSA (n=6): 5.84±0.02; MS275 (n=7): 5.87±0.03; P <0.05 vs . Baseline], without any significant changes in maximally activated force. Similar increase in calcium sensitivity was also observed when skinned fibers were incubated overnight in a buffer containing acetyl-CoA [acetyl-CoA (n=6): 5.84±0.04; P <0.05 vs . Baseline]. These observations suggest that acetylation of myofilament proteins can regulate myofilament calcium sensitivity. Western blot analyses of skinned fibers revealed that HDAC4 and HDAC5 were specifically associated with myofilament proteins, and acetylation of several myofilament proteins was increased following TSA treatment. One of these acetylated proteins was identified as muscle LIM protein (MLP). Protein-protein interaction analyses and co-localization studies showed that MLP specifically binds to HDAC4. Functional studies with skinned fibers isolated from MLP knock out [MLP −/− ] mice (C57BL6 strain) indicated that TSA-induced increase in calcium sensitivity was completely prevented [MLP −/− -Baseline (n=6): 5.60±0.03; MLP −/− -TSA (n=6): 5.61±0.02; P <NS] compared to wild-type (WT) mice of the same strain [WT-Baseline (n=6): 5.59±0.02; WT-TSA (n=6): 5.70±0.02; P <0.05]. These data demonstrate, for the first time, that class-II HDACs bind to cardiac myofilament proteins, with MLP being one of the binding partners, and play a role in regulating myofilament contractile function.

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