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

2000 ◽  
Vol 88 (1) ◽  
pp. 91-101 ◽  
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.

Evidence that signal transduction for osmoreception is mediated by stretch-activated ion channels in tilapia

2003 ◽  
Vol 284 (5) ◽  
pp. C1290-C1296 ◽  
Author(s):  
A. P. Seale ◽  
N. H. Richman ◽  
T. Hirano ◽  
I. Cooke ◽  
E. G. Grau
Keyword(s):  
Ion Channels ◽  
Channel Blocker ◽  
Oreochromis Mossambicus ◽  
Cell Swelling ◽  
Simultaneous Measurements ◽  
Perfusion Chamber ◽  
Intracellular Ca ◽  
Stretch Activated Ion Channels

Prolactin (PRL) plays a central role in the freshwater osmoregulation of teleost fish, including the tilapia ( Oreochromis mossambicus). Consistent with this action, PRL release from the tilapia pituitary increases as extracellular osmolality is reduced both in vitro and in vivo. Dispersed tilapia PRL cells were incubated in a perfusion chamber that allowed simultaneous measurements of cell volume and PRL release. Intracellular Ca2+ concentrations were measured from fura 2-loaded PRL cells treated in a similar way. Gadolinium (Gd3+), known to block stretch-activated cation channels, inhibited hyposmotically induced PRL release in a dose-related manner without preventing cell swelling. Nifedipine, an L-type Ca2+ channel blocker, did not prevent the increase in PRL release during hyposmotic stimulation. A high, depolarizing concentration of KCl induced a transient and marked increase of intracellular Ca2+ and release of PRL but did not prevent the rise in intracellular Ca2+ and PRL release evoked by exposure to hyposmotic medium. These findings suggest that a decrease in extracellular osmolality stimulates PRL release through the opening of stretch-activated ion channels, which allow extracellular Ca2+ to enter the cell when it swells.

scholarly journals TRPV4 is the temperature-sensitive ion channel of human sperm

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nadine Mundt ◽  
Marc Spehr ◽  
Polina V Lishko
Keyword(s):  
Ion Channels ◽  
Human Sperm ◽  
Cytosolic Calcium ◽  
Membrane Depolarization ◽  
K Channel ◽  
Temperature Sensitive ◽  
Downstream Signaling ◽  
Protein Levels ◽  
Cation Conductance ◽  
Initial Membrane

Ion channels control the ability of human sperm to fertilize the egg by triggering hyperactivated motility, which is regulated by membrane potential, intracellular pH, and cytosolic calcium. Previous studies unraveled three essential ion channels that regulate these parameters: (1) the Ca2+ channel CatSper, (2) the K+ channel KSper, and (3) the H+ channel Hv1. However, the molecular identity of the sperm Na+ conductance that mediates initial membrane depolarization and, thus, triggers downstream signaling events is yet to be defined. Here, we functionally characterize DSper, the Depolarizing Channel of Sperm, as the temperature-activated channel TRPV4. It is functionally expressed at both mRNA and protein levels, while other temperature-sensitive TRPV channels are not functional in human sperm. DSper currents are activated by warm temperatures and mediate cation conductance, that shares a pharmacological profile reminiscent of TRPV4. Together, these results suggest that TRPV4 activation triggers initial membrane depolarization, facilitating both CatSper and Hv1 gating and, consequently, sperm hyperactivation.

scholarly journals TRPV4 is the temperature-sensitive ion channel of human sperm

2018 ◽  
Author(s):  
Nadine Mundt ◽  
Marc Spehr ◽  
Polina V. Lishko
Keyword(s):  
Ion Channels ◽  
Human Sperm ◽  
Cytosolic Calcium ◽  
Membrane Depolarization ◽  
Temperature Sensitive ◽  
Downstream Signaling ◽  
Protein Levels ◽  
Cation Conductance ◽  
Trpv Channels ◽  
Initial Membrane

AbstractIon channels control sperm fertilizing ability by triggering hyperactivated motility, which is regulated by membrane potential, intracellular pH, and cytosolic calcium. Previous studies unraveled three essential ion channels that regulate these parameters: 1) the Ca2+ channel CatSper, 2) the K+ channel KSper, and 3) the H+ channel Hv1. However, the molecular identity of an additional sperm Na+ conductance that mediates initial membrane depolarization and, thus, triggers downstream signaling events is yet to be defined. Here, we functionally characterize DSper, the Depolarizing Channel of Sperm, as the temperature-activated channel TRPV4. It is functionally expressed at both mRNA and protein levels, while other temperature-sensitive TRPV channels are not functional in human sperm. DSper currents are activated by warm temperatures and mediate cation conductance, that shares a pharmacological profile reminiscent of TRPV4. Together, these results suggest that TRPV4 activation triggers initial membrane depolarization, facilitating both CatSper and Hv1 gating and, consequently, sperm hyperactivation.

Stretch-activated ion channels and c-fos expression remain active after repeated eccentric bouts

2003 ◽  
Vol 94 (6) ◽  
pp. 2296-2302 ◽  
Author(s):  
Todd A. McBride
Keyword(s):  
Ion Channels ◽  
Contractile Force ◽  
Resting Membrane Potential ◽  
Similar Degree ◽  
Rat Skeletal Muscle ◽  
Muscle Weight ◽  
Transcript Levels ◽  
Multiple Exposures ◽  
Training Response ◽  
Stretch Activated Ion Channels

This study was undertaken to measure the response of stretch-activated ion channels (SAC) and transcript levels of the oncogene c- fos to separate bouts of eccentric contractions (EC). It was hypothesized that SAC in rat skeletal muscle would contribute to resting membrane potential depolarization after separate repeated bouts of EC. Blockage of SAC during an EC training regime also tested the necessity of SAC for a training response. It was also hypothesized that transcript levels of c- fos would be maximally elevated after the first exposure to EC and diminish with repeated exposures. The results indicate less depolarization after multiple bouts of EC, which could be reversed by blocking the SAC. Transcript levels of c- fos were elevated to a similar degree after either a single or multiple exposures to EC. EC training resulted in significant increases in contractile force and muscle wet and dry weights in nontreated animals. Training in the presence of the SAC-blocker streptomycin produced similar changes in contractile force without changes in muscle weight. SAC and c- fos are activated after several exposures to EC and therefore remain as possible signals in EC training responses.

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

2019 ◽  
Vol 20 (5) ◽  
pp. 1165 ◽  
Author(s):  
Sergey Tyganov ◽  
Timur Mirzoev ◽  
Boris Shenkman
Keyword(s):  
Ion Channels ◽  
Potential Role ◽  
Hindlimb Unloading ◽  
Eccentric Contractions ◽  
Temporal Response ◽  
Mtorc1 Signaling ◽  
Mechanical Signal ◽  
Rat Soleus Muscle ◽  
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.

Primary involvement of K+ conductance in membrane resonance of trigeminal root ganglion neurons

1988 ◽  
Vol 59 (1) ◽  
pp. 77-89 ◽  
Author(s):  
E. Puil ◽  
B. Gimbarzevsky ◽  
I. Spigelman
Keyword(s):  
Electrical Properties ◽  
Channel Blocker ◽  
Complex Impedance ◽  
Membrane Potentials ◽  
K Channel ◽  
Bathing Medium ◽  
Trigeminal Root ◽  
Membrane Resonance ◽  
Ganglion Neurons ◽  
Impedance Magnitude

1. The complex impedances and impedance magnitude functions were obtained from neurons in in vitro slices of trigeminal root ganglia using frequency-domain analyses of intracellularly recorded voltage responses to specified oscillatory input currents. A neuronal model derived from linearized Hodgkin-Huxley-like equations was used to fit the complex impedance data. This procedure yielded estimates for membrane electrical properties. 2. Membrane resonance was observed in the impedance magnitude functions of all investigated neurons at their initial resting membrane potentials and was similar to that reported previously for trigeminal root ganglion neurons in vivo. Tetrodotoxin (10(-6) M), a Na+-channel blocker, applied in the bathing medium for 20 min produced only minor changes, if any, in the resonance, although gross impairment of Na+-spike electrogenesis was apparent in most of the neurons. Brief applications (1-5 min) of a K+-channel blocker, tetraethylammonium (TEA; 10(-2) M), increased the impedance magnitude and abolished, in a reversible manner, the resonant behavior. In all cases, the resonant frequency was decreased by TEA administration prior to total blockade of resonance. 3. The TEA-induced blockade of resonance was associated with decreases in the estimates of the membrane conductances, without significant alterations of input capacitance. A particularly large decrease was observed in Gr, the time-invariant resting conductance that includes a lumped leak conductance component. The voltage- and time-dependent conductance, GL, and associated relaxation time constant, tau u, also declined progressively during administration of TEA. 4. Systematic variations in the membrane potentials of trigeminal root ganglion neurons were produced by intracellular injections of long-lasting step currents with superposition of the oscillatory current stimuli, in order to assess the effects of TEA on the relationship of the electrical properties to the membrane potential. Applications of TEA led to a depolarizing shift in the dependence of the membrane property estimates, suggesting voltage-dependence of the effects of TEA on presumed K+ channels in the membrane. 5. These data suggest a primary involvement of K+ conductance in the genesis of membrane resonance. This electrical behavior or its ionic mechanism is a major modulator of the subthreshold electrical responsiveness of trigeminal root ganglion neurons.

scholarly journals Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation

1999 ◽  
Vol 277 (3) ◽  
pp. L558-L565 ◽  
Author(s):  
Scott A. Barman
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Channel Blocker ◽  
Pressor Response ◽  
Vascular Occlusion ◽  
Membrane Depolarization ◽  
Delayed Rectifier ◽  
Vascular Compliance ◽  
Kinase C ◽  
Pkc Activation

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10−7 M) and thymeleatoxin (THX; 10−7 M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10−5 M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10−4 M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10−5 M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

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

2002 ◽  
Vol 282 (4) ◽  
pp. H1334-H1340 ◽  
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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