Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice

Liu, Xueru; Tan, Xiaoqiu; Yang, Yan; Zeng, Xiaorong; Tang, Xian-ling

doi:10.1038/aps.2011.134

Cited by 9 publications

(3 citation statements)

References 35 publications

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“…Activation of BK Ca channels elicits the infarct-sparing effects of late ischemic preconditioning in myocardial I/R injury in animal models ( Wang et al, 2010 ). Liu X.R. et al (2012) suggested that propofol causes greater vasodilating effects by increasing the Ca 2+ sensitivity of BK Ca channel in the cerebral arterial smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial BKCa Mediates the Protective Effect of Low-Dose Ethanol Preconditioning on Oxygen-Glucose Deprivation and Reperfusion-Induced Neuronal Apoptosis

Yang

Guo

et al. 2021

Front. Physiol.

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Ischemia-reperfusion (I/R) injury contributes to the morbidity and mortality of ischemic strokes. As an in vitro model, oxygen-glucose deprivation and reperfusion (OGD/R) exposure induces neuronal injury. Low-dose ethanol preconditioning (EtOH-PC) was reported to alleviate neuronal apoptosis during OGD/R. However, whether the mitochondrial BKCa (mitoBKCa) channel is involved in the neuroprotective effect of EtOH-PC during OGD/R is not clearly defined. This study attempts to explore the mediation of the mitoBKCa channel in the neuroprotective effect of EtOH-PC on OGD/R-induced neuronal apoptosis and the underlying mechanisms. OGD/R model was established using primary cortical neurons that were preincubated with ethanol. Subsequently, the cell viability was measured by CCK-8 assay, and the apoptotic cells were determined by TUNEL assay. Annexin V/7-AAD staining and mitochondrial membrane potential using JC-10 were detected by flow cytometry. Western blot analysis was performed to check the apoptosis-related proteins. In the mixed primary culture, 95% neurofilament-positive cells were cortical neurons. Low-dose EtOH-PC (10 mmol/L) for 24 h significantly attenuated the OGD2h/R24h-induced neuronal apoptosis through activating the BKCa channel. Further investigations suggested that ethanol pretreatment increased the mitochondrial membrane potential (MMP) and downregulated the production of cleaved caspase 3 in OGD/R-injured neurons by activating the mitoBKCa channel. Low-dose ethanol pretreatment significantly attenuated the OGD/R-induced neuronal apoptosis mediated by the mitoBKCa channel which modulated the mitochondrial function by impeding the uncontrolled opening of mitochondrial permeability transition pore (MPTP).

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Section: Discussionmentioning

confidence: 99%

Mitochondrial BKCa Mediates the Protective Effect of Low-Dose Ethanol Preconditioning on Oxygen-Glucose Deprivation and Reperfusion-Induced Neuronal Apoptosis

Yang

Guo

et al. 2021

Front. Physiol.

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“…The development of chronic hypertension could be attributed to the decrease in blood vessel elasticity induced by long-term excessive contraction [ 4 ]. Under such a pathophysiological condition, propofol, with its potent vasodilative effect, can switch the state of blood vessels from overcontraction to excessive relaxation [ 5 ]. Eventually, patients with chronic hypertension have abrupt fluctuations in blood pressure and usually experience long-term hypotension because of the deterioration of vascular elasticity.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of connexin 43-based gap junctions underlies propofol-induced excessive relaxation in hypertensive vascular smooth muscle cells

et al. 2023

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Background Postinduction hypotension caused by propofol remains a non-negligible problem for anesthesiologists, and is especially severe in chronic hypertensive patients with long-term vasoconstriction and decreased vascular elasticity. The functional change in gap junctions composed of Cx43 (Cx43-GJs) is reported as the biological basis of synchronized contraction or relaxation of blood vessels. Thus, we investigated the role of Cx43-GJs in propofol-induced dramatic blood pressure fluctuations in chronic hypertensive patients, and their internal mechanisms. Methods Human umbilical artery smooth muscle cells (HUASMCs) were pretreated with long-term angiotensin II (Ang II), with or without propofol, to simulate the contraction and relaxation of normal and hypertensive VSMCs during anesthesia induction. The levels of F-actin polymerization and MLC2 phosphorylation were used as indicators to observe the contraction and relaxation of HUASMCs. Different specific activators, inhibitors and siRNAs were used to explore the role of Cx43-GJs and Ca2+ as well as the RhoA/ LIMK2/cofilin and RhoA/MLCK signaling pathways in the contraction and relaxation of normal and hypertensive HUASMCs. Results Both F-actin polymerization and MLC2 phosphorylation were significantly enhanced in Ang II-pretreated HUASMCs, along with higher expression of Cx43 protein and stronger function of Cx43-GJs than in normal HUASMCs. However, with propofol administration, similar to Gap26 and Cx43-siRNA, the function of Cx43-GJs in Ang II-pretreated HUASMCs was inhibited compared with that in normal HUASMCs, accompanied by a larger decrease in intracellular Ca2+ and the RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways. Eventually F-actin polymerization and MLC2 phosphorylation were more dramatically decreased. However, these effects could be reversed by RA with enhanced Cx43-GJ function. Conclusion Long-term exposure to Ang II significantly enhanced the expression of the Cx43 protein and function of Cx43-GJs in HUASMCs, resulting in the accumulation of intracellular Ca2+ and the activation of its downstream RhoA/LIMK2/cofilin and RhoA/MLCK signaling pathways, which maintained HUASMCs in a state of excessive-contraction. With inhibition of Cx43-GJs by propofol in Ang II-pretreated HUASMCs, intracellular Ca2+ and its downstream signaling pathways were dramatically inhibited, which ultimately excessively relaxed HUASMCs. This is the reason why the blood pressure fluctuation of patients with chronic hypertension was more severe after receiving propofol induction.

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“…Furthermore, patients with vena cava collapse are prone to develop significant hypotension when treated with propofol, which may be a direct result of vascular relaxation ( 1 – 4 ). Certain studies have indicated that propofol elicits vascular relaxation via the following mechanisms: i) Activation of large-conductance calcium voltage-activated potassium channels (BK Ca ) ( 2 ); ii) activation of ATP-sensitive K + channels (K ATP ) ( 5 ); iii) inhibition of voltage-operated calcium channels and receptor-operated calcium channels ( 6 ); and iv) increases in the availability of nitric oxide ( 7 , 8 ). Propofol may cause vasodilation via four different pathways, however, to the best of our knowledge, no experimental study has assessed the mechanism of vasodilation induced by propofol on the rat mesenteric artery.…”

Section: Introductionmentioning

confidence: 99%

Propofol‑induced vasodilation of mesenteric arterioles via BKCa channel and gap junction

Wan

Wang

et al. 2018

Exp Ther Med

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The present study aimed to investigate the role of propofol in mediating the vasomotor activity of the mesenteric arteriole (MA) of Sprague Dawley (SD) rats, and to elucidate the underlying mechanisms. The pressure myograph technique was used to examine the effect of different concentrations of propofol on the relaxation of blood vessels in the 2–3 mm MA segments freshly separated from the SD rats. The whole-cell patch-clamp technique was applied to observe the outward current of single vascular smooth muscle cells (VSMCs) obtained from the MAs of the SD rats. Furthermore, immunofluorescence was utilized to assess the expression of connexin (Cx) in the MAs of SD rats. The results indicated the following: i) Propofol relaxed the MA of SD rats in a concentration-dependent manner from 1×10−7 to 3×10−4 mol/l; ii) in the acutely dissociated VSMCs, propofol (1×10−7 to 3×10−4 mol/l) enhanced the outward current of VSMCs in a concentration-dependent manner; iii) the enhanced outward currents induced by propofol (1×10−5 mol/l) may be reversed by tetraethylammonium (TEA; 1 mmol/l), a calcium-activated K+ channel inhibitor; iv) the effect of propofol on the relaxation of the vasculature wAS reduced after perfusion with 1 mmol/l TEA; v) Cx40, Cx43 and Cx45 were expressed on the MA; 6) 18β-glycyrrhetintic acid and 2-aminoethoxydiphenyl borate, two types of gap junction blocker, inhibited the propofol-induced relaxation. The present study provides evidence that propofol relaxes the MA, which may be associated with its effect of enhancing the channel current of large-conductance calcium voltage-activated potassium channels, contributing to the K+ outflow and leading to VSMC hyperpolarization; the gap junction may facilitate the hyperpolarization, which may lead to vascular synchronized relaxation and thereby reduce the blood pressure.

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Propofol increases the Ca2+ sensitivity of BKCa in the cerebral arterial smooth muscle cells of mice

Cited by 9 publications

References 35 publications

Mitochondrial BKCa Mediates the Protective Effect of Low-Dose Ethanol Preconditioning on Oxygen-Glucose Deprivation and Reperfusion-Induced Neuronal Apoptosis

Mitochondrial BKCa Mediates the Protective Effect of Low-Dose Ethanol Preconditioning on Oxygen-Glucose Deprivation and Reperfusion-Induced Neuronal Apoptosis

Downregulation of connexin 43-based gap junctions underlies propofol-induced excessive relaxation in hypertensive vascular smooth muscle cells

Propofol‑induced vasodilation of mesenteric arterioles via BKCa channel and gap junction

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