An Anabolic Signaling Response of Rat Soleus Muscle to Eccentric Contractions Following Hindlimb Unloading: A Potential Role of Stretch-Activated Ion Channels

Mechanisms that convert a mechanical signal into a biochemical response in an atrophied skeletal muscle remain poorly understood. The aims of the study were to evaluate a temporal response of anabolic signaling and protein synthesis (PS) to eccentric contractions (EC) in rat soleus during hindlimb unloading (HU); and to assess a possible role of stretch-activated ion channels (SAC) in the propagation of a mechanical signal to mTORC1 following HU. Following HU, an isolated soleus was subjected to EC. Upon completion of EC, muscles were collected for western blot analyses to determine the content/phosphorylation of the key anabolic markers. We found that a degree of EC-induced p70S6K phosphorylation and the rate of PS in the soleus of 3- and 7-day unloaded rats was significantly less than that in control. A decrease in EC-induced phosphorylation of p70S6K, RPS6 and PS in the 7-day unloaded soleus treated with SAC inhibitor did not differ from that of the 7-day unloaded soleus without SAC blockade. The results of the study suggest that (i) HU results in a blunted anabolic response to a bout of EC, (ii) attenuation of mTORC1-signaling and PS in response to EC in unloaded soleus may be associated with inactivation of SAC.

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Acute recovery from disuse atrophy: the role of stretch-activated ion channels in the activation of anabolic signaling in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00261.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. E86-E95 ◽

Cited By ~ 2

Author(s):

Timur M. Mirzoev ◽

Sergey A. Tyganov ◽

Irina O. Petrova ◽

Boris S. Shenkman

Keyword(s):

Ion Channels ◽

Time Course ◽

Glycogen Synthase ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Hindlimb Suspension ◽

Disuse Atrophy ◽

Mtorc1 Signaling ◽

Stretch Activated Ion Channels

The aim of the study was to 1) measure time-course alternations in the rate of protein synthesis (PS) and phosphorylation status of the key anabolic markers, and 2) find out the role of stretch-activated ion channels (SACs) in the activation of anabolic signaling in the rat soleus during an acute reloading following disuse atrophy. Wistar rats were subjected to 14-day hindlimb suspension (HS) followed by 6, 12, and 24 h of reloading. To examine the role of SAC in the reloading-induced activation of anabolic signaling, the rats were treated with gadolinium (Gd3+), a SAC blocker. The content of signaling proteins was determined by Western blot. c-Myc mRNA expression was assessed by RT-PCR. After 24-h reloading, the PS rate was elevated by 44% versus control. After 6-h reloading, the p-70-kDa ribosomal protein S6 kinase (p70S6k) and translation initiation factor 4E-binding protein 1 (4E-BP1) did not differ from control; however, 12-h reloading resulted in an upregulation of both p70s6k and 4E-BP1 phosphorylation versus control. The phosphorylation of AKT (Ser473) and glycogen synthase kinase-3β (Ser9) was reduced after HS and then completely restored by 12-h reloading. c-Myc was significantly upregulated during the entire reloading. Gd3+ treatment during reloading (12 h) prevented a full phosphorylation of p70S6k, rpS6, 4E-BP1, as well as PS activation. The results of the study suggest that 1) enhanced PS during the acute recovery from HS may be associated with the activation of ribosome biogenesis as well as mammalian target of rapamycin complex 1 (mTORC1)-dependent signaling pathways, and 2) functional SACs are necessary for complete activation of mTORC1 signaling in rat soleus during acute recovery from HS.

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Increased coronary perfusion augments cardiac contractility in the rat through stretch-activated ion channels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00327.2001 ◽

2002 ◽

Vol 282 (4) ◽

pp. H1334-H1340 ◽

Cited By ~ 16

Author(s):

R. R. Lamberts ◽

M. H. P. van Rijen ◽

P. Sipkema ◽

P. Fransen ◽

S. U. Sys ◽

...

Keyword(s):

Ion Channels ◽

Perfusion Pressure ◽

Cardiac Contractility ◽

No Synthase ◽

Coronary Perfusion ◽

Channel Blockade ◽

No Release ◽

Sustained Increase ◽

Stretch Activated Ion Channels

The role of stretch-activated ion channels (SACs) in coronary perfusion-induced increase in cardiac contractility was investigated in isolated isometrically contracting perfused papillary muscles from Wistar rats. A brief increase in perfusion pressure (3–4 s, perfusion pulse, n = 7), 10 repetitive perfusion pulses ( n = 4), or a sustained increase in perfusion pressure (150–200 s, perfusion step, n = 7) increase developed force by 2.7 ± 1.1, 7.7 ± 2.2, and 8.3 ± 2.5 mN/mm2 (means ± SE, P < 0.05), respectively. The increase in developed force after a perfusion pulse is transient, whereas developed force during a perfusion step remains increased by 5.1 ± 2.5 mN/mm2 ( P < 0.05) in the steady state. Inhibition of SACs by addition of gadolinium (10 μmol/l) or streptomycin (40 and 100 μmol/l) blunts the perfusion-induced increase in developed force. Incubation with 100 μmol/l N ω-nitro-l-arginine [nitric oxide (NO) synthase inhibition], 10 μmol/l sodium nitroprusside (NO donation) and 0.1 μmol/l verapamil (L-type Ca2+ channel blockade) are without effect on the perfusion-induced increase of developed force. We conclude that brief, repetitive, or sustained increases in coronary perfusion augment cardiac contractility through activation of stretch-activated ion channels, whereas endothelial NO release and L-type Ca2+channels are not involved.

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Stretch-activated ion channels contribute to membrane depolarization after eccentric contractions

Journal of Applied Physiology ◽

10.1152/jappl.2000.88.1.91 ◽

2000 ◽

Vol 88 (1) ◽

pp. 91-101 ◽

Cited By ~ 75

Author(s):

Todd A. McBride ◽

Bradley W. Stockert ◽

Fredric A. Gorin ◽

Richard C. Carlsen

Keyword(s):

Ion Channels ◽

Channel Blocker ◽

Contractile Function ◽

Muscle Fibers ◽

Membrane Depolarization ◽

Membrane Potentials ◽

Eccentric Contractions ◽

Multiple Exposures ◽

Cation Conductance ◽

Stretch Activated Ion Channels

We tested the hypothesis that eccentric contractions activate mechanosensitive or stretch-activated ion channels (SAC) in skeletal muscles, producing increased cation conductance. Resting membrane potentials and contractile function were measured in rat tibialis anterior muscles after single or multiple exposures to a series of eccentric contractions. Each exposure produced a significant and prolonged (>24 h) membrane depolarization in exercised muscle fibers. The magnitude and duration of the depolarization were related to the number of contractions. Membrane depolarization was due primarily to an increase in Na+ influx, because the estimated Na+-to-K+ permeability ratio was increased in exercised muscles and resting membrane potentials could be partially repolarized by substituting an impermeant cation for extracellular Na+ concentration. Neither the Na+/H+ antiport inhibitor amiloride nor the fast Na+ channel blocker TTX had a significant effect on the depolarization. In contrast, addition of either of two nonselective SAC inhibitors, streptomycin or Gd3+, produced significant membrane repolarization. The results suggest that muscle fibers experience prolonged depolarization after eccentric contractions due, principally, to the activation of Na+-selective SAC.

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The potential role of mechanosensitive ion channels in substrate stiffness-regulated Ca2+ response in chondrocytes

Connective Tissue Research ◽

10.1080/03008207.2021.2007902 ◽

2021 ◽

pp. 1-10

Author(s):

Genlai Du ◽

Weiyi Chen ◽

Li Li ◽

Quanyou Zhang

Keyword(s):

Ion Channels ◽

Potential Role ◽

Substrate Stiffness ◽

Mechanosensitive Ion Channels

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Sa2052 Role of Stretch-Activated Ion Channels in Esophageal Inhibitory Motor Neurons

Gastroenterology ◽

10.1016/s0016-5085(14)61319-6 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-364

Author(s):

Hui Dong ◽

Yanfen Jiang ◽

Ravinder K. Mittal

Keyword(s):

Ion Channels ◽

Motor Neurons ◽

Inhibitory Motor Neurons ◽

Stretch Activated Ion Channels

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Responsiveness of vascular endothelium to shear stress: potential role of ion channels and cellular cytoskeleton (review).

International Journal of Molecular Medicine ◽

10.3892/ijmm.4.4.323 ◽

1999 ◽

Cited By ~ 2

Author(s):

A I Barakat

Keyword(s):

Shear Stress ◽

Ion Channels ◽

Vascular Endothelium ◽

Potential Role ◽

Cellular Cytoskeleton

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Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: role of stretch-activated ion channels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1992.262.4.h1110 ◽

1992 ◽

Vol 262 (4) ◽

pp. H1110-H1115 ◽

Cited By ~ 33

Author(s):

W. Sigurdson ◽

A. Ruknudin ◽

F. Sachs

Keyword(s):

Ion Channels ◽

Calcium Release ◽

Heart Cells ◽

Mechanical Stimuli ◽

Extracellular Medium ◽

Fluorescent Response ◽

Chick Heart ◽

Calcium Induced Calcium Release ◽

Stretch Activated Ion Channels

Heart rate and contractility are sensitive to stretch. To better understand the origin of these effects, we have studied the effect of mechanical stimuli on a model system of tissue-cultured heart cells. Gently prodding cells with a pipette produced a Ca2+ influx that often led to waves of calcium-induced calcium release (CICR) spreading from the site of stimulation. Ca2+ release could also be produced by pulling on neighboring cells. The response was blocked by removing extracellular Ca2+ or by adding 20 microM Gd3+ to normal saline. The mechanical sensitivity probably arose from stretch-activated ion channels (SACs) based on several lines of evidence. Chick heart cells contain nonselective cation SACs that pass Ca2+ as well as Na+ and K+. Both the SACs and the fluorescence response are blocked by 20 microM Gd3+. Removal of Ca2+ from the extracellular medium blocked the fluorescent response. Cultures without SACs (grown in the absence of embryo extract) had no mechanically induced fluxes. These data contradict the recent claim that SAC activity is a patch-clamp artifact (C.E. Morris and R. Horn, Science Wash. DC 256: 1246-1249, 1991). The SACs had a density of approximately 1/micron 2 and were expected to pass less than 20 fA of Ca2+ current under physiological conditions. The change in intracellular concentration of Ca2+ ([Ca2+]i) resulting from activation of SACs may be too small to induce CICR unless the channels pass current into a restricted space (N. LeBlanc and J.R. Hume, Science Wash. DC 248: 372, 1990).(ABSTRACT TRUNCATED AT 250 WORDS)

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