Angiotensin II mobilizes intracellular calcium and activates pannexin‐1 channels in rat carotid body type II cells via AT<sub>1</sub> receptors

Murali, Sindhubarathi; Zhang, Min; Nurse, Colin A.

doi:10.1113/jphysiol.2014.279299

Cited by 47 publications

(99 citation statements)

References 41 publications

(212 reference statements)

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“…Because this phenomenon also remained unaffected by staurosporine, a phosphorylation event appears to be an unlikely cause. The mechanisms leading to current enhancement could include a reactive alkalization of the cytoplasm or an increase in cytoplasmic calcium ion concentration (9,34).…”

Section: Discussionmentioning

confidence: 99%

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

Krick¹,

Wang

St-Pierre³

et al. 2016

Journal of Biological Chemistry

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ATP is a key regulator of the innate pulmonary host defense by activating purinergic P2Y2 receptors, which promote chloride secretion by calcium-activated Cl Ϫ channels, inhibit Na ϩ absorption by epithelial Na ϩ channels, increase ciliary beat frequency and airway surface liquid volume, and induce mucin release, thereby activating mucociliary clearance (1-4).Although the effects of ATP on airway epithelial cells have been studied widely, Panx1 channels have only been recognized recently to be involved in ATP release in these tissues (5, 6). Mechanical stress has been shown to be one of the prime stimuli to increase the ATP concentration on the airway surface to a concentration sufficient to activate P2Y2 receptors (7). This ATP release was neither dependent on the intracellular calcium concentration, excluding an exocytotic release mechanism, nor caused by the cystic fibrosis transmembrane conductance regulator. In previous studies, we were the first to show that Panx1, an ortholog of the invertebrate innexin, is expressed at the apical membrane of airway epithelia, contributing to ATP release (5).Pannexin proteins form pannexons, which are channels that open at resting membrane potential because of mechanical stress and in response to extracellular ATP when co-expressed with P2Y2 receptors (8, 9). In addition to stimulated ATP release, resting ATP levels on the apical surface reflect a steady state that, depending on its range, can help autoregulate the release or metabolism of ATP.Currently little is known about the physiological regulation of pannexin channels in the airway epithelium. Most studies have been performed on oocytes or transfected HEK cells. These studies demonstrated that ATP itself is a potent regulator by increasing the permeability of Panx1 initially when coexpressed with P2Y2 receptors but, consequently, causing inhibition as a feedback loop (10, 11).The cytokine IFN-␥ is produced in inflammatory airway diseases such as severe asthma (12, 13) and chronic bronchitis with and without airflow obstruction (14). We have shown that IFN-␥ can increase H 2 O 2 production via increased expression of Duox2, a member of the NADPH oxidase gene family, in ALI 2 cultures (15, 16). In addition to H 2 O 2 , Duox also releases cytosolic H ϩ (17), which could contribute to intracellular acidification. Consequently, a decrease in intracellular pH could decrease mucociliary function by direct inhibition of the ciliary beat frequency (18). In fact, Duox is up-regulated in chronic bronchitis and patients with smoke exposure (15,19,20). Preliminary data also suggested that intracellular pH is essential in

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Section: Discussionmentioning

confidence: 99%

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

Krick¹,

Wang

St-Pierre³

et al. 2016

Journal of Biological Chemistry

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“…A direct physical interaction is indicated by co-immunoprecipitation for Panx1 and the P2X7 receptor [63] or the potassium channel subunit Kvb3 [67]. Furthermore, Panx1 can be activated by glutamate binding to NMDA receptors, by noradrenaline through alpha adrenergic receptors, or by angiotensin II binding to AT1 receptors [68][69][70]. The interaction of Panx1 with Kvb3 is intriguing, as the pharmacology of the pannexon is changed by this interaction.…”

Section: Expression and Function Of Pannexons In The Central Nervous mentioning

confidence: 99%

“…( j) Angiotensin II-induced ATP release is inhibited by intracellular calcium chelation with BAPTA and thus pannexon activation could be a direct consequence of the rise in intracellular [Ca 2þ ] [70].…”

Section: Activation Of Pannexons In Physiological and Pathological Comentioning

confidence: 99%

ATP release through pannexon channels

Dahl

2015

Phil. Trans. R. Soc. B

203

169

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One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Extracellular adenosine triphosphate (ATP) serves as a signal for diverse physiological functions, including spread of calcium waves between astrocytes, control of vascular oxygen supply and control of ciliary beat in the airways. ATP can be released from cells by various mechanisms. This review focuses on channel-mediated ATP release and its main enabler, Pannexin1 (Panx1). Six subunits of Panx1 form a plasma membrane channel termed 'pannexon'. Depending on the mode of stimulation, the pannexon has large conductance (500 pS) and unselective permeability to molecules less than 1.5 kD or is a small (50 pS), chloride-selective channel. Most physiological and pathological stimuli induce the large channel conformation, whereas the small conformation so far has only been observed with exclusive voltage activation of the channel. The interaction between pannexons and ATP is intimate. The pannexon is not only the conduit for ATP, permitting ATP efflux from cells down its concentration gradient, but the pannexon is also modulated by ATP. The channel can be activated by ATP through both ionotropic P2X as well as metabotropic P2Y purinergic receptors. In the absence of a control mechanism, this positive feedback loop would lead to cell death owing to the linkage of purinergic receptors with apoptotic processes. A control mechanism preventing excessive activation of the purinergic receptors is provided by ATP binding (with low affinity) to the Panx1 protein and gating the channel shut.

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“…Hypoxia causes secretion of many transmitters from glomus cells and these include dopamine, acetylcholine (ACh), ATP, endothelin, nitric oxide and serotonin [44,46]. Among these, ACh and ATP are thought to be the primary transmitters that increase afferent carotid sinus nerve activity [66].…”

Section: Role Of Task In Autoregulation Of Transmitter Secretion In Gmentioning

confidence: 99%

Role of K2P channels in stimulus-secretion coupling

Kim

Kang

2014

Pflugers Arch - Eur J Physiol

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Two-pore domain K+ (K2P) channels are involved in a variety of physiological processes by virtue of their high basal activity and sensitivity to various biological stimuli. One of these processes is secretion of hormones and transmitters in response to stimuli such as hypoxia, acidosis and receptor agonists. The rise in intracellular [Ca2+] ([Ca2+]i) that is critical for the secretory event can be achieved by several mechanisms: (a) Inhibition of resting (background) K+ channels, (b) activation of Na+/Ca2+-permeable channels and (c) release of Ca2+ from intracellular stores. Here, we discuss the role of TASK and TREK in stimulus-secretion mechanisms in carotid body chemoreceptor cells and adrenal medullary/cortical cells. Studies show that stimuli such as hypoxia and acidosis cause cell depolarization and transmitter/hormone secretion by inhibition of TASK or TREK. Subsequent elevation of [Ca2+]i produced by opening of voltage-dependent Ca2+ channels then activates a Na+-permeable cation channel, presumably to help sustain the depolarization and [Ca2+]i. Agonists such as angiotensin II may elevate [Ca2+]i via multiple mechanisms involving both inhibition of TASK/TREK and Ca2+ release from internal stores to cause aldosterone secretion. Thus, inhibition of resting (background) K+ channels and subsequent activation of voltage-gated Ca2+ channels and Na+-permeable non-selective cation channels may be a common ionic mechanism that lead to hormone and transmitter secretion.

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Angiotensin II mobilizes intracellular calcium and activates pannexin‐1 channels in rat carotid body type II cells via AT₁ receptors

Cited by 47 publications

References 41 publications

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

ATP release through pannexon channels

Role of K2P channels in stimulus-secretion coupling

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Angiotensin II mobilizes intracellular calcium and activates pannexin‐1 channels in rat carotid body type II cells via AT1 receptors

Cited by 47 publications

References 41 publications

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production

ATP release through pannexon channels

Role of K2P channels in stimulus-secretion coupling

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Angiotensin II mobilizes intracellular calcium and activates pannexin‐1 channels in rat carotid body type II cells via AT₁ receptors