Altered acetylcholine, bradykinin and cutaneous pressure‐induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link

Garry, Ambroise; Fromy, Bérengère; Blondeau, Nicolas; Henrion, Didier; Brau, Frédéric; Gounon, Pierre; Guy, Nicolas; Heurteaux, Catherine; Lazdunski, Michel; Saumet, J. L.

doi:10.1038/sj.embor.7400916

Cited by 78 publications

(69 citation statements)

References 38 publications

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“…The channel was also detected in mesenteric arteries (110,111). In these vessels of TREK-1 Ϫ/Ϫ mice, the myogenic vasoconstriction (in response to elevated intravascular pressure) and the effect of adrenergic stimulation, which directly activates VSMCs, were maintained.…”

Section: Cerebrovascular and Mesenteric Vasodilation Bymentioning

confidence: 73%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

752

769

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Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2P channel types) that this primary hyperpolarizing action is not performed passively. The K2P channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2P channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2P channel family into the spotlight. In this review, we focus on the physiological roles of K2P channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

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Section: Cerebrovascular and Mesenteric Vasodilation Bymentioning

confidence: 73%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

752

769

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“…Furthermore, TREK-1 gene-deficient mice exhibit reduced touch sensitivity (2), providing in vivo evidence for neuronal mechanosensation. Although TREK-1 was not involved in myogenic vasoconstriction in mesenteric arteries, TREK-1 plays a role for pressure-induced vasodilatation in the skin (33), highlighting distinct mechanosensory mechanisms in different tissues.…”

Section: Potentially Mechanosensitive Ion Channelsmentioning

confidence: 91%

G protein-mediated stretch reception

Storch¹,

Schnitzler

Gudermann

2012

American Journal of Physiology-Heart and Circulatory Physiology

154

136

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Mechanosensation and -transduction are important for physiological processes like the senses of touch, hearing, and balance. The mechanisms underlying the translation of mechanical stimuli into biochemical information by activating various signaling pathways play a fundamental role in physiology and pathophysiology but are only poorly understood. Recently, G protein-coupled receptors (GPCRs), which are essential for the conversion of light, olfactory and gustatory stimuli, as well as of primary messengers like hormones and neurotransmitters into cellular signals and which play distinct roles in inflammation, cell growth, and differentiation, have emerged as potential mechanosensors. The first candidate for a mechanosensitive GPCR was the angiotensin-II type-1 (AT 1) receptor. Agonist-independent mechanical receptor activation of AT 1 receptors induces an active receptor conformation that appears to differ from agonist-induced receptor conformations and entails the activation of G proteins. Mechanically induced AT 1 receptor activation plays an important role for myogenic vasoconstriction and for the initiation of cardiac hypertrophy. A growing body of evidence suggests that other GPCRs are involved in mechanosensation as well. These findings highlight physiologically relevant, ligand-independent functions of GPCRs and add yet another facet to the polymodal activation spectrum of this ubiquitous protein family. mechanosensation; G protein-coupled receptor; angiotensin-II type-1 receptor; agonist independent THIS ARTICLE is part of a collection on G Protein Kinase A Signaling in Cardiovascular Physiology and Disease. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology. org/.

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“…Deletion of the TREK-1 channel was shown to be associated with an impairment in the cascade producing NO, leading to endothelial dysfunction. 11 In cerebral basilar arteries, the deletion of TREK-1 does not alter smooth muscle vasodilation in response to the NO-donor SNP, but it abolishes the response to ACh. These new observations are in line with our previous work.…”

mentioning

confidence: 99%

Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel

Blondeau

Pétrault

Manta

et al. 2007

Circulation Research

Self Cite

112

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Abstract-Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially ␣-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly ␣-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. ␣-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1 Ϫ/Ϫ mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as ␣-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia. (Circ Res. 2007;101:176-184.) Key Words: cerebral ischemia Ⅲ ␣-linolenic acid Ⅲ CBF Ⅲ vasodilatation Ⅲ two pore-domains channel TREK-1 A fter stroke, the function of cerebral arteries is critical to maintain cerebral perfusion and preserve neuronal integrity. The duration and intensity of the blood flow deficit are associated with the severity of brain damage. The level of cerebral blood flow (CBF) in brain tissue is coupled to an evident extent with vascular function and beyond neuronal consequences. It is well known that cerebral ischemia is associated with functional impairment of vascular tone within the occluded artery. 1 Polyunsaturated fatty acids (PUFAs) and particularly ␣-linolenic acid (ALA) and docosahexanoic acid (DHA) are potent protectors against focal and global ischemia. [2][3][4] The molecular mechanism of PUFA-induced neuroprotection has been recently clarified. 5 The main PUFA target seems to be the potassium channel, TREK-1, which belongs to the new family of two-pore domain potassium channels (K 2P ) and is known to be potently activated by PUFA. 6 -8 The importance of the TREK-1 channel in cerebral protection against ischemia has been validated by the fact that the protective effects of PUFA are drastically decreased in TREK-1-deficient mice. 5 The vascular wall represents the primary compartment of ischemic stroke. PUFA application confers neuronal protection, 2-4 but little is known about TREK-1 channel in cerebral vessels. A previous report shows the presence ...

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Altered acetylcholine, bradykinin and cutaneous pressure‐induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link

Cited by 78 publications

References 38 publications

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

G protein-mediated stretch reception

Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel

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Altered acetylcholine, bradykinin and cutaneous pressure‐induced vasodilation in mice lacking the TREK1 potassium channel: the endothelial link

Cited by 78 publications

References 38 publications

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

G protein-mediated stretch reception

Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel

Contact Info

Product

Resources

About

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels