Pharmacological profiling of stretch activated channels in proprioceptive neurons

2020 ◽  
Vol 233 ◽  
pp. 108765
Author(s):  
Shelby McCubbin ◽  
Anna Jeoung ◽  
Courtney Waterbury ◽  
Robin L. Cooper
Keyword(s):  
Stretch Activated Channels

Epithelial Na Channels and Their Kin

Physiology ◽  
1995 ◽  
Vol 10 (2) ◽  
pp. 61-67 ◽  
Author(s):  
LG Palmer
Keyword(s):  
Na Channels ◽  
Epithelial Na Channels ◽  
Mechanical Sensing ◽  
Stretch Activated Channels

Epithelial Na channels help maintain Na homeostasis by controlling the rate of Na absorption by the kidney and other organs. Surprisingly, they show homology with genes involved in mechanical sensing and transduction. This suggests that epithelial Na channels and stretch-activated channels may be in the same family.

Mechanisms of regulatory volume decrease in UC-11MG human astrocytoma cells

1993 ◽  
Vol 264 (5) ◽  
pp. C1201-C1209 ◽  
Author(s):  
S. Medrano ◽  
E. Gruenstein
Keyword(s):  
Brain Injuries ◽  
Regulatory Volume Decrease ◽  
Transport Pathways ◽  
Astrocytoma Cells ◽  
Hypotonic Treatment ◽  
Human Astrocytoma ◽  
Stretch Activated Channels ◽  
Human Astrocytoma Cells ◽  
Volume Decrease

Swelling of astrocytes commonly occurs after cerebral ischemia and other brain injuries. Because these cells constitute 20-25% of human brain volume, their swelling is a major factor in the morbidity and mortality associated with cerebral edema. Many cells, including astrocytes, resist or reverse the tendency to swell by activating transport pathways that lead to a regulatory volume decrease. Here we report the results of studies designed to elucidate the mechanisms of the regulatory volume decrease that occurs after astrocytes are swollen by exposure to hypotonic medium. Using UC-11MG cells, a well-characterized, human, astrocytoma-derived line, we observed an increase in membrane permeability to both K+ and Cl- during regulatory volume decrease, consistent with a net loss of these ions. Neither the increase in K+ exit nor the regulatory volume decrease was affected by bumetanide, an inhibitor of anion-cation cotransport. On the other hand, the increased K+ efflux, as well as the regulatory volume decrease, was blocked by Gd3+, suggesting a putative role of stretch-activated cationic channels in the process of volume regulation. Although increases in intracellular free Ca2+ were also observed during hypotonic treatment, they occurred well after the onset of the regulatory volume decrease. Furthermore, the regulatory volume decrease was not affected by blocking the intracellular free Ca2+ increase with dimethyl 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid or by removal of extracellular Ca2+. These results indicate that the regulatory volume decrease in UC-11MG cells may involve stretch-activated channels that operate independently of changes in intracellular free Ca2+.

Gadolinium and mechanotransduction of rat aortic baroreceptors

1992 ◽  
Vol 262 (5) ◽  
pp. H1415-H1421 ◽  
Author(s):  
M. C. Andresen ◽  
M. Yang
Keyword(s):  
Ion Channels ◽  
Direct Effects ◽  
Cellular Mechanisms ◽  
Pressure Discharge ◽  
Ethanesulfonic Acid ◽  
Discharge Pressure ◽  
Aortic Baroreceptors ◽  
Stretch Activated Channels ◽  
Stretch Activated Ion Channels

The cellular mechanisms enabling baroreceptors to transduce wall distortion into axonal discharge are unknown but might involve stretch-activated ion channels. Gadolinium (Gd3+, 10 microM) blocks stretch-activated channels in several preparations. Here we tested Gd3+ effects on discharge responses of 15 single-fiber baroreceptors in vitro. We simultaneously measured discharge, pressure, and aortic diameter at Gd3+ concentrations from 0.001 to 400 microM. High levels of Gd3+ added to a bicarbonate-buffered perfusate (Krebs) slightly shifted the pressure-discharge relation (less than 4 mmHg, n = 3, P = 0.01) without affecting slope or discharge frequency at threshold. Gd3+ in Krebs variably altered the pressure-diameter relation. Because 500 microM Gd3+ produced visible precipitate in Krebs, we tested Gd3+ in a simpler perfusate using N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES). Gd3+ in HEPES (n = 10) induced minor, but statistically significant, average increases in threshold (less than +5-7%) and no changes in gain. However, prolonged HEPES exposure alone (n = 2) produced similar shifts. Electron microscopy verified that Gd3+ diffused from the lumen to reach extracellular locations near baroreceptor endings. We conclude that 1) HEPES perfusate alone reversibly depresses baroreceptor discharge and 2) Gd3+ has no direct effects on baroreceptors. Thus it appears that aortic baroreceptor mechanotransduction must utilize a different class of stretch-activated ion channels.

Modulation of cardiac Na+ current by gadolinium, a blocker of stretch-induced arrhythmias

2001 ◽  
Vol 280 (1) ◽  
pp. H272-H279 ◽  
Author(s):  
Gui-Rong Li ◽  
Clive M. Baumgarten
Keyword(s):  
Cell Voltage ◽  
Inactivation Kinetics ◽  
Na Current ◽  
Threshold Potential ◽  
Current Voltage ◽  
Slope Factor ◽  
Altered Surface ◽  
Maximum Conductance ◽  
Stretch Activated Channels ◽  
Antiarrhythmic Efficacy

Gd3+ blocks stretch-activated channels and suppresses stretch-induced arrhythmias. We used whole cell voltage clamp to examine whether effects on Na+ channels might contribute to the antiarrhythmic efficacy of Gd3+. Gd3+ inhibited Na+ current ( I Na) in rabbit ventricle (IC50 = 48 μM at −35 mV, holding potential −120 mV), and block increased at more negative test potentials. Gd3+ made the threshold for I Na more positive and reduced the maximum conductance. Gd3+ (50 μM) shifted the midpoints for activation and inactivation of I Na 7.9 and 5.7 mV positive but did not alter the slope factor for either relationship. Activation and inactivation kinetics were slowed in a manner that could not be explained solely by altered surface potential. Paradoxically, Gd3+ increased I Naunder certain conditions. With membrane potential held at −75 mV, Gd3+ still shifted threshold for activation positive, but I Na increased positive to −40 mV, causing the current-voltage curves to cross over. When availability initially was low, increased availability induced by Gd3+ dominated the response at test potentials positive to −40 mV. The results indicate that Gd3+ has complex effects on cardiac Na+channels. Independent of holding potential, Gd3+ is a potent I Na blocker near threshold potential, and inhibition of I Na by Gd3+ is likely to contribute to suppression of stretch-induced arrhythmias.

Ca2+ uptake in GH3 cells during hypotonic swelling: the sensory role of stretch-activated ion channels

1996 ◽  
Vol 270 (6) ◽  
pp. C1790-C1798 ◽  
Author(s):  
Y. Chen ◽  
S. M. Simasko ◽  
J. Niggel ◽  
W. J. Sigurdson ◽  
F. Sachs
Keyword(s):  
Volume Regulation ◽  
Cell Swelling ◽  
Gh3 Cells ◽  
Membrane Tension ◽  
Hypotonic Cell Swelling ◽  
Stretch Activated Channels ◽  
Ca2 Channels ◽  
Hypotonic Swelling ◽  
Volume Decrease

Hypotonic cell swelling triggers an increase in intracellular Ca2+ concentration that is deemed responsible for the subsequent regulated volume decrease in many cells. To understand the mechanisms underlying this increase, we have studied the Ca2+ sources that contribute to hypotonic cell swelling-induced Ca2+ increase (HICI) in GH3 cells. Fura 2 fluorescence of cell populations revealed that extracellular, but not intracellular, stores of Ca2+ were required. HICI was abolished by nifedipine, a blocker of L-type Ca2+ channels, and Gd3+, a nonspecific blocker of stretch-activated channels (SACs), suggesting two components for the Ca2+ membrane pathway: L-type Ca2+ channels and SACs. Using HICI as an assay, we found that venom from the spider Grammostola spatulata could block HICI without blocking L-type Ca2+ channels. The venom did, however, block SAC activity. This suggests that Ca(2+)-permeable SACs, rather than L-type Ca2+ channels, are the sensing elements for HICI. These results support the model for volume regulation in which SACs, activated by an increase of the membrane tension during hypotonic cell swelling, trigger HICI, leading to a volume decrease.

Effects of Ca2+ channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats

2006 ◽  
Vol 291 (5) ◽  
pp. H2187-H2191 ◽  
Author(s):  
Toru Kawada ◽  
Toji Yamazaki ◽  
Tsuyoshi Akiyama ◽  
Kazunori Uemura ◽  
Atsunori Kamiya ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Acetylcholine Release ◽  
Local Administration ◽  
Ach Release ◽  
Parasympathetic Nerve ◽  
Nonselective Cation Channels ◽  
Voltage Dependent ◽  
Stretch Activated Channels ◽  
Postganglionic Nerve

Although an axoplasmic Ca2+ increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca2+ channels in ACh release in the mammalian cardiac parasympathetic nerve is not clearly understood. Using a cardiac microdialysis technique, we examined the effects of Ca2+ channel antagonists on vagal nerve stimulation- and ischemia-induced myocardial interstitial ACh releases in anesthetized cats. The vagal stimulation-induced ACh release [22.4 nM (SD 10.6), n = 7] was significantly attenuated by local administration of an N-type Ca2+ channel antagonist ω-conotoxin GVIA [11.7 nM (SD 5.8), n = 7, P = 0.0054], or a P/Q-type Ca2+ channel antagonist ω-conotoxin MVIIC [3.8 nM (SD 2.3), n = 6, P = 0.0002] but not by local administration of an L-type Ca2+ channel antagonist verapamil [23.5 nM (SD 6.0), n = 5, P = 0.758]. The ischemia-induced myocardial interstitial ACh release [15.0 nM (SD 8.3), n = 8] was not attenuated by local administration of the L-, N-, or P/Q-type Ca2+ channel antagonists, by inhibition of Na+/Ca2+ exchange, or by blockade of inositol 1,4,5-trisphosphate [Ins( 1 , 4 , 5 )P3] receptor but was significantly suppressed by local administration of gadolinium [2.8 nM (SD 2.6), n = 6, P = 0.0283]. In conclusion, stimulation-induced ACh release from the cardiac postganglionic nerves depends on the N- and P/Q-type Ca2+ channels (with a dominance of P/Q-type) but probably not on the L-type Ca2+ channels in cats. In contrast, ischemia-induced ACh release depends on nonselective cation channels or cation-selective stretch activated channels but not on L-, N-, or P/Q type Ca2+ channels, Na+/Ca2+ exchange, or Ins( 1 , 4 , 5 )P3 receptor-mediated pathway.

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