Correction: Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure

Mackay, Charles; Leo, M Dennis; Fernández‐Peña, Carlos; Hasan, Raquibul; Yin, Wen; Mata-Daboin, Alejandro; Bulley, Simon; Gammons, Jesse; Mancarella, Salvatore; Jaggar, Jonathan H.

doi:10.7554/elife.60401

Cited by 9 publications

(12 citation statements)

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“…Mesenteric artery bed was dissected and placed in pre-chilled PSS. Third and fourth order branches of mesenteric arteries (<250 μm) were cleaned of adventitial tissue, cut into 1–2 mm long segments, and cannulated for pressure myography [ 24 , 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…Use of a low intravascular pressure of 40 mmHg allowed us to maintain a pure PE-induced constriction model without additional signaling characteristic of myogenic vasoconstriction. Vessel diameter was read at 1 Hz using a CCD camera connected to a Nikon Ts2 microscope, coupled with the edge-detection function of IonWizard software (IonOptix, Milton, MA, USA) [ 24 , 25 , 26 , 27 ]. Where needed, endothelium denudation was achieved by slow passage of air bubbles through the vessel lumen.…”

Section: Methodsmentioning

confidence: 99%

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Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Hasan

Menon

Zerin

et al. 2022

Heliyon

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Hasan

Menon

Zerin

et al. 2022

Heliyon

Self Cite

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“…Third and fourth order branches of mesenteric arteries (150–250 µm) were dissected cleaned of adventitial tissue in ice-cold PSS. Cleaned arterial branches were cut into 1–2 mm long segments that were kept in ice-cold PSS until cannulated for pressure myography [ 39 , 40 , 41 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

“…Luminal flow was absent during the experiment. Myogenic tone (%) was calculated as follows: 100 × (1 − D active /D passive ), where D active is active arterial diameter in the presence of Ca 2+ and D passive is the passive arterial diameter determined in Ca 2+ -free PSS supplemented with 5 mM EGTA [ 39 , 40 , 41 , 57 ].…”

Section: Methodsmentioning

confidence: 99%

Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels

Hasan

2021

IJMS

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The antidiabetic drug empagliflozin is reported to produce a range of cardiovascular effects, including a reduction in systemic blood pressure. However, whether empagliflozin directly modulates the contractility of resistance-size mesenteric arteries remains unclear. Here, we sought to investigate if empagliflozin could relax resistance-size rat mesenteric arteries and the associated underlying molecular mechanisms. We found that acute empagliflozin application produces a concentration-dependent vasodilation in myogenic, depolarized and phenylephrine (PE)-preconstricted mesenteric arteries. Selective inhibition of smooth muscle cell voltage-gated K+ channels KV1.5 and KV7 abolished empagliflozin-induced vasodilation. In contrast, pharmacological inhibition of large-conductance Ca2+-activated K+ (BKCa) channels and ATP-sensitive (KATP) channels did not abolish vasodilation. Inhibition of the vasodilatory signaling axis involving endothelial nitric oxide (NO), smooth muscle cell soluble guanylyl cyclase (sGC) and protein kinase G (PKG) did not abolish empagliflozin-evoked vasodilation. Inhibition of the endothelium-derived vasodilatory molecule prostacyclin (PGI2) had no effect on the vasodilation. Consistently, empagliflozin-evoked vasodilation remained unaltered by endothelium denudation. Overall, our data suggest that empagliflozin stimulates smooth muscle cell KV channels KV1.5 and KV7, resulting in vasodilation in resistance-size mesenteric arteries. This study demonstrates for the first time a novel mechanism whereby empagliflozin regulates arterial contractility, resulting in vasodilation. Due to known antihypertensive properties, treatment with empagliflozin may complement conventional antihypertensive therapy.

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“… 10 In contrast, K Ca 2.3 channels seem to co-localize with mechanosensitive or receptor-operated transient receptor potential (TRP) cation channels. 10 , 11 Ca 2+ influx through these cation channels may activate K Ca 2.3 channels. The outflow of K + can hyperpolarize ET cells, increase the inward electrochemical gradient for Ca 2+ , and augment the Ca 2+ influx, which in turn enhances nitric oxide (NO) releases.…”

Section: Introductionmentioning

confidence: 99%

Subtype-Selective Positive Modulation of K_Ca2.3 Channels Increases Cilia Length

et al. 2022

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Small-conductance Ca 2+ -activated potassium (K Ca 2.x) channels are gated exclusively by intracellular Ca 2+ . The activation of K Ca 2.3 channels induces hyperpolarization, which augments Ca 2+ signaling in endothelial cells. Cilia are specialized Ca 2+ signaling compartments. Here, we identified compound 4 that potentiates human K Ca 2.3 channels selectively. The subtype selectivity of compound 4 for human K Ca 2.3 over rat K Ca 2.2a channels relies on an isoleucine residue in the HA/HB helices. Positive modulation of K Ca 2.3 channels by compound 4 increased flow-induced Ca 2+ signaling and cilia length, while negative modulation by AP14145 reduced flow-induced Ca 2+ signaling and cilia length. These findings were corroborated by the increased cilia length due to the expression of Ca 2+ -hypersensitive K Ca 2.3_G351D mutant channels and the reduced cilia length resulting from the expression of Ca 2+ -hyposensitive K Ca 2.3_I438N channels. Collectively, we were able to associate functions of K Ca 2.3 channels and cilia, two crucial components in the flow-induced Ca 2+ signaling of endothelial cells, with potential implications in vasodilation and ciliopathic hypertension.

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Correction: Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure

Cited by 9 publications

References 0 publications

Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels

Subtype-Selective Positive Modulation of K_Ca2.3 Channels Increases Cilia Length

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Correction: Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure

Cited by 9 publications

References 0 publications

Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Dapagliflozin induces vasodilation in resistance-size mesenteric arteries by stimulating smooth muscle cell KV7 ion channels

Empagliflozin Relaxes Resistance Mesenteric Arteries by Stimulating Multiple Smooth Muscle Cell Voltage-Gated K+ (KV) Channels

Subtype-Selective Positive Modulation of KCa2.3 Channels Increases Cilia Length

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Subtype-Selective Positive Modulation of K_Ca2.3 Channels Increases Cilia Length