K+ depolarization induces RhoA kinase translocation to caveolae and Ca<sup>2+</sup> sensitization of arterial muscle

Urban, Nicole H.; Berg, Krystina M.; Ratz, Paul H.

doi:10.1152/ajpcell.00501.2002

Cited by 102 publications

(108 citation statements)

References 49 publications

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“…In the present study, the Rho-kinase inhibitor Y-27632 dose dependently reduced the contraction but not the increase in [Ca 2ϩ ] i induced by KCl, which suggests that Rho kinase is involved in Ca 2ϩ sensitization evoked by depolarization and confirms previous reports in arterial smooth muscle from several vascular beds (15,24,32). The inhibitory effect of Y-27632 on the contractions of both [Ca 2ϩ ]-clamped ␣-toxin-permeabilized arteries and on those induced by K ϩ depolarization in intact arteries suggests that both Ca 2ϩ -independent and -dependent mechanisms, respectively, are involved in the Rho kinase-mediated Ca 2ϩ sensitization.…”

Section: Discussionsupporting

confidence: 92%

“…Although Rho kinase is activated by excitatory agonists via receptors coupled to the G ␣12/13 family of heterotrimeric G proteins (10), recent studies have demonstrated that Ca 2ϩ sensitization involving Rho-kinase activation can also be brought about by membrane depolarization (15,24,32). In the present study, the Rho-kinase inhibitor Y-27632 dose dependently reduced the contraction but not the increase in [Ca 2ϩ ] i induced by KCl, which suggests that Rho kinase is involved in Ca 2ϩ sensitization evoked by depolarization and confirms previous reports in arterial smooth muscle from several vascular beds (15,24,32).…”

Section: Discussionmentioning

confidence: 99%

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Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Villalba¹,

Stankevičius²,

Simonsen³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca 2ϩ sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca 2ϩ entry induced by ␣1-adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca 2ϩ ([Ca 2ϩ ]i) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca 2ϩ ]i and tension elicited by the ␣1-adrenoceptor agonist phenylephrine (Phe). In contrast, the protein kinase C (PKC) inhibitor Ro-31-8220 reduced tension without altering the Phe-induced increase in [Ca 2ϩ ]i. In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca 2ϩ signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca 2ϩ entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba 2ϩ influx stimulated by Phe in fura-2 AM-loaded arteries. The addition of Y-27632 to arteries depolarized with high KCl markedly reduced tension without changing [Ca 2ϩ ]i. In ␣-toxin-permeabilized penile arteries stimulated with threshold Ca 2ϩ concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5Ј-O-(3-thiotriphosphate) (GTP␥S) or Phe in the presence of GTP␥S. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca 2ϩ . These results suggest that Rho kinase, besides its contribution to the Ca 2ϩ sensitization of the contractile proteins, is also involved in the regulation of Ca 2ϩ entry through a nonselective cation channel activated by ␣1-adenoceptor stimulation in rat penile arteries. penile arteries; calcium entry; nonselective cation channels; calcium sensitization PENILE ERECTION OCCURS when nitric oxide (NO) released from nerves and endothelium upon sexual stimulation relaxes smooth muscle of the corpus cavernosum (CC) and penile arteries, leading to blood filling of the sinuses and restriction of venous outflow (2, 25). During the flaccid state, erectile tissue is contracted by the release of neural and local factors, such as norepinephrine, neuropeptide Y, endothelin-1, and prostanoids that increase smooth muscle cytosolic Ca 2ϩ ([Ca 2ϩ ] i ) and/or Ca 2ϩ sensitization through activation G protein-coupled receptors (2,20,25). Erectile dysfunction (ED), considered as a sign of early endothelial dysfunction and cardiovascular disease, is three times more prevalent in men with Types 1 and 2 diabetes than in men without diabetes (3, 33). About 50% of these patients exhibit suboptimal responses to oral phophodiestarase 5 inhibitors, such as sildenafil (33), that enhance the NOmediated vasodilatation leading to penile erection. As an alternative, inhibition of the Rho/Rho-kinase signaling pathway has been proposed as a potential molecular target for the development of novel therapies for ED si...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Villalba¹,

Stankevičius²,

Simonsen³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…RhoA and Rho kinase exhibit activity-dependent translocation to caveolae (62,65), suggesting a role for cholesterol depletion-induced changes in caveolae organization. Interestingly, caveolae are also sensitive to cell volume perturbations (46), and have been implicated in VRAC regulation (63,64).…”

Section: Discussionmentioning

confidence: 99%

“…In vascular endothelial cells (7,42) and NIH3T3 cells (47) the activity of the Rho-associated kinase (Rho kinase; ROK) is required for VRAC activation. RhoA and ROK associate with rafts and caveola and translocate to caveolae in an activationdependent manner (62,65), raising the possibility that the effect of cholesterol depletion on VRAC might involve changes in Rho kinase activity.…”

mentioning

confidence: 99%

Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin

Klausen

Hougaard²,

Hoffmann³

et al. 2006

American Journal of Physiology-Cell Physiology

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The mechanisms controlling the volume-regulated anion current (VRAC) are incompletely elucidated. Here, we investigate the modulation of VRAC by cellular cholesterol and the potential involvement of F-actin, Rho, Rho kinase, and phosphatidylinositol-(4,5)-bisphosphate [PtdIns(4,5)P2] in this process. In Ehrlich-Lettre ascites (ELA) cells, a current with biophysical and pharmacological properties characteristic of VRAC was activated by hypotonic swelling. A 44% increase in cellular cholesterol content had no detectable effects on F-actin organization or VRAC activity. A 47% reduction in cellular cholesterol content increased cortical and stress fiber-associated F-actin content in swollen cells. Cholesterol depletion increased VRAC activation rate and maximal current after a modest (15%), but not after a severe (36%) reduction in extracellular osmolarity. The cholesterol depletion-induced increase in maximal VRAC current was prevented by F-actin disruption using latrunculin B (LB), while the current activation rate was unaffected by LB, but dependent on Rho kinase. Rho activity was decreased by ∼20% in modestly, and ∼50% in severely swollen cells. In modestly swollen cells, this reduction was prevented by cholesterol depletion, which also increased isotonic Rho activity. Thrombin, which stimulates Rho and causes actin polymerization, potentiated VRAC in modestly swollen cells. VRAC activity was unaffected by inclusion of a water-soluble PtdIns(4,5)P2 analogue or a PtdIns(4,5)P2-blocking antibody in the pipette, or neomycin treatment to sequester PtdIns(4,5)P2. It is suggested that in ELA cells, F-actin and Rho-Rho kinase modulate VRAC magnitude and activation rate, respectively, and that cholesterol depletion potentiates VRAC at least in part by preventing the hypotonicity-induced decrease in Rho activity and eliciting actin polymerization.

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“…KClevoked contraction has been linked to the activation of Rho kinase (Urban et al, 2003). Moreover, Rho kinase has also been implicated in events leading to Ca 2+ entry in vascular muscle distinct from voltage-or store-operated channels in rat aorta and mesenteric arteries (Ghisdal et al, 2003).…”

Section: Other Signaling Pathwaysmentioning

confidence: 99%

Potassium-induced intermittent vasomotion in rat isolated pulmonary artery

Bieger

Ford

Tabrizchi

2011

J. Smooth Muscle Res.

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A novel intermittent vasomotion induced by potassium in rat pulmonary artery was investigated with a view to characterize the ion channel mechanisms governing such secondary oscillatory activity. Isometric force was recorded from ring preparations of rat isolated pulmonary arteries incubated in a modified Krebs buffer containing K ]e. Our findings support the concept that a secondary vasomotive oscillator operates in rat pulmonary artery which enables the activity of the primary oscillator to be regulated in a cyclic manner via sarcolemmal L-type Ca 2+ channels and an array of K conductances.

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K+ depolarization induces RhoA kinase translocation to caveolae and Ca²⁺ sensitization of arterial muscle

Cited by 102 publications

References 49 publications

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin

Potassium-induced intermittent vasomotion in rat isolated pulmonary artery

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K+ depolarization induces RhoA kinase translocation to caveolae and Ca2+ sensitization of arterial muscle

Cited by 102 publications

References 49 publications

Rho kinase is involved in Ca2+ entry of rat penile small arteries

Rho kinase is involved in Ca2+ entry of rat penile small arteries

Cholesterol modulates the volume-regulated anion current in Ehrlich-Lettre ascites cells via effects on Rho and F-actin

Potassium-induced intermittent vasomotion in rat isolated pulmonary artery

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Product

Resources

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K+ depolarization induces RhoA kinase translocation to caveolae and Ca²⁺ sensitization of arterial muscle

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries

Rho kinase is involved in Ca²⁺ entry of rat penile small arteries