MaxiK potassium channels in the function of chemoreceptor cells of the rat carotid body

2009 ◽  
Vol 297 (3) ◽  
pp. C715-C722 ◽  
Author(s):  
Angela Gomez-Niño ◽  
Ana Obeso ◽  
Jose Antonio Baranda ◽  
Jaime Santo-Domingo ◽  
Jose Ramon Lopez-Lopez ◽  
...  
Keyword(s):  
Carotid Body ◽  
Acute Hypoxia ◽  
Channel Blockers ◽  
Intracellular Ca ◽  
Weakly Inward ◽  
Chemoreceptor Cells ◽  
Cell Depolarization ◽  
Pore Domain ◽  
Maxik Channels ◽  
Maxik Channel

Hypoxia activates chemoreceptor cells of the carotid body (CB) promoting an increase in their normoxic release of neurotransmitters. Catecholamine (CA) release rate parallels the intensity of hypoxia. Coupling of hypoxia to CA release requires cell depolarization, produced by inhibition of O2-regulated K+ channels, and Ca2+ entering the cells via voltage-operated channels. In rat chemoreceptor cells hypoxia inhibits large-conductance, calcium-sensitive K channels (maxiK) and a two-pore domain weakly inward rectifying K+ channel (TWIK)-like acid-sensitive K+ channel (TASK)-like channel, but the significance of maxiK is controversial. A proposal envisions maxiK contributing to set the membrane potential ( Em) and the hypoxic response, but the proposal is denied by authors finding that maxiK inhibition does not depolarize chemoreceptor cells or alters intracellular Ca2+ concentration or CA release in normoxia or hypoxia. We found that maxiK channel blockers (tetraethylammonium and iberiotoxin) did not modify CA release in rat chemoreceptor cells, in either normoxia or hypoxia, and iberiotoxin did not alter the Ca2+ transients elicited by hypoxia. On the contrary, both maxiK blockers increased the responses elicited by dinitrophenol, a stimulus we demonstrate does not affect maxiK channels in isolated patches of rat chemoreceptor cells. We conclude that in rat chemoreceptor cells maxiK channels do not contribute to the genesis of the Em, and that their full inhibition by hypoxia, preclude further inhibition by maxiK channel blockers. We suggest that full inhibition of this channel is required to generate the spiking behavior of the cells in acute hypoxia.

Participation of Na+ channels in the response of carotid body chemoreceptor cells to hypoxia

1994 ◽  
Vol 267 (3) ◽  
pp. C738-C744 ◽  
Author(s):  
A. Rocher ◽  
A. Obeso ◽  
M. T. Cachero ◽  
B. Herreros ◽  
C. Gonzalez
Keyword(s):  
Carotid Body ◽  
Neurotransmitter Release ◽  
Marked Reduction ◽  
Adult Rabbit ◽  
Na Channels ◽  
Na Current ◽  
Chemoreceptor Cells ◽  
Cell Depolarization ◽  
First Time ◽  
Mild Hypoxia

The role played by Na+ channels of carotid body (CB) chemoreceptor cells was investigated by studying the effects of tetrodotoxin (TTX) on the release of 3H-labeled catecholamines ([3H]CA) by adult rabbit CBs previously incubated with the precursor [3H]tyrosine. TTX inhibited partially the release of [3H]CA elicited by mild hypoxia (10 or 7% O2) or by depolarizing incubation medium containing 20 or 30 mM KCl, but the response to more intense hypoxia (5 or 2% O2) or to higher KCl concentration (40 or 50 mM) was not significantly affected. The release of [3H]CA elicited by acidic stimuli, either 20% CO2 (pH 6.6) or the protonophore dinitrophenol (100 microM), although comparable in magnitude to that elicited by mild hypoxia, was not modified by TTX. These results provide evidence for the first time that Na+ channels of chemoreceptor cells participate in the transduction of hypoxic stimuli into the neurotransmitter release response of these cells and suggest that Na+ current operates as an amplifying device that enhances the initial cell depolarization mediated by the closure of the O2-sensitive K+ channels. Sympathetic denervation of CBs was followed by a marked reduction in the release of [3H]CA elicited by veratridine or by 20 mM KCl, suggesting that the number of Na+ channels in chemoreceptor cells decreases after denervation.

Intracellular Ca2+ stores in chemoreceptor cells of the rabbit carotid body: significance for chemoreception

2000 ◽  
Vol 279 (1) ◽  
pp. C51-C61 ◽  
Author(s):  
I. Vicario ◽  
A. Obeso ◽  
A. Rocher ◽  
J. R. López-Lopez ◽  
C. González
Keyword(s):  
Significant Role ◽  
Carotid Body ◽  
Time Course ◽  
Cyclopiazonic Acid ◽  
Structural Identity ◽  
High K ◽  
Intracellular Ca ◽  
Intact Rabbit ◽  
Chemoreceptor Cells

The notion that intracellular Ca2+ (Cai 2+) stores play a significant role in the chemoreception process in chemoreceptor cells of the carotid body (CB) appears in the literature in a recurrent manner. However, the structural identity of the Ca2+ stores and their real significance in the function of chemoreceptor cells are unknown. To assess the functional significance of Cai 2+ stores in chemoreceptor cells, we have monitored 1) the release of catecholamines (CA) from the cells using an in vitro preparation of intact rabbit CB and 2) the intracellular Ca2+ concentration ([Ca2+]i) using isolated chemoreceptor cells; both parameters were measured in the absence or the presence of agents interfering with the storage of Ca2+. We found that threshold [Ca2+]i for high extracellular K+ (Ke +) to elicit a release response is ≈250 nM. Caffeine (10–40 mM), ryanodine (0.5 μM), thapsigargin (0.05–1 μM), and cyclopiazonic acid (10 μM) did not alter the basal or the stimulus (hypoxia, high Ke +)-induced release of CA. The same agents produced Cai 2+transients of amplitude below secretory threshold; ryanodine (0.5 μM), thapsigargin (1 μM), and cyclopiazonic acid (10 μM) did not alter the magnitude or time course of the Cai 2+responses elicited by high Ke +. Several potential activators of the phospholipase C system (bethanechol, ATP, and bradykinin), and thereby of inositol 1,4,5-trisphosphate receptors, produced minimal or no changes in [Ca2+]i and did not affect the basal release of CA. It is concluded that, in the rabbit CB chemoreceptor cells, Cai 2+ stores do not play a significant role in the instant-to-instant chemoreception process.

Effects of low glucose on carotid body chemoreceptor cell activity studied in cultures of intact organs and in dissociated cells

2012 ◽  
Vol 302 (8) ◽  
pp. C1128-C1140 ◽  
Author(s):  
Teresa Gallego-Martin ◽  
Silvia Fernandez-Martinez ◽  
Ricardo Rigual ◽  
Ana Obeso ◽  
Constancio Gonzalez
Keyword(s):  
Glucose Homeostasis ◽  
Carotid Body ◽  
Cell Activity ◽  
Fluorescent Signal ◽  
Intracellular Ca ◽  
Dissociated Cells ◽  
Wavelength Emission ◽  
Low Glucose ◽  
Chemoreceptor Cells ◽  
Cells Cultured

The participation of the carotid body (CB) in glucose homeostasis and evidence obtained in simplified cultured CB slices or dissociated cells have led to the proposal that CB chemoreceptor cells are glucoreceptors. However, data generated in intact, freshly excised organs deny CB chemoreceptor cells' glucosensing properties. The physiological significance of the contention has prompted the present study, performed in a newly developed preparation of the intact CB organ in culture that maintains chemoreceptor cells' microenvironment. Chemoreceptor cells of intact CBs in culture retained their capacity to store, synthesize, and secrete catecholamine in response to hypoxia for at least 6 days. Aglycemia did not elicit neurosecretion in dissociated chemoreceptor cells or in intact CB in culture, but potentiated hypoxia-elicited neurosecretion, exclusively, in 1-day-old intact CB cultures and dissociated chemoreceptor cells cultured for 24 h. In fura 2-loaded cells, aglycemia (but not 1 mM) caused a slow Ca2+-dependent and nifedipine-insensitive increase in fluorescence at 340- to 380-nm wavelength emission ratio and augmented the fluorescent signal elicited by hypoxia. Association of nifedipine and KBR7943 (a Na+/Ca2+ exchanger inhibitor) completely abolished the aglycemic Ca2+ response. We conclude that chemoreceptor cells are not sensitive to hypoglycemia. We hypothesize that cultured chemoreceptor cells become transiently more dependent on glycolysis. Consequently, aglycemia would partially inhibit the Na+/K+ pump, causing an increase in intracellular Na+ concentration, and a reversal of Na+/Ca2+ exchanger. This would slowly increase intracellular Ca2+ concentration and cause the potentiation of the hypoxic responses. We discuss the nature of the signals detected by chemoreceptor cells for the CB to achieve its glycemic homeostatic role.

Postnatal development of E-4031-sensitive potassium current in rat carotid chemoreceptor cells

2005 ◽  
Vol 98 (4) ◽  
pp. 1469-1477 ◽  
Author(s):  
Insook Kim ◽  
Kathleen M. Boyle ◽  
John L. Carroll
Keyword(s):  
Carotid Body ◽  
Type I ◽  
Body Type ◽  
Type I Cells ◽  
Intracellular Ca ◽  
Old Rats ◽  
Cell Depolarization ◽  
Perforated Patch Clamp ◽  
I Cells ◽  
In Cells

The O2 sensitivity of dissociated type I cells from rat carotid body increases with age until ∼14–16 days. Hypoxia-induced depolarization appears to be mediated by an O2-sensitive K+ current, but other K+ currents may modulate depolarization. We hypothesized that membrane potential may be stabilized in newborn type I cells by human ether-a-go-go-related gene (HERG)-like K+ currents that inhibit hypoxia-induced depolarization and that a decrease in this current with age could underlie, in part, the developmental increase in type I cell depolarization response to hypoxia. In dissociated type I cells from 0- to 1- and 11- to 16-day-old rats, using perforated patch-clamp and 70 mM K+ extracellular solution, we measured repolarization-induced inward K+ tail currents in the absence and presence of E-4031, a specific HERG channel blocker. This allowed isolation of the E-4031-sensitive HERG-like current. E-4031-sensitive peak currents in type I cells from 0- to- 1-day-old rats were 2.5-fold larger than in cells from 11- to 16-day-old rats. E-4031-sensitive current density in newborn type I cells was twofold greater than in cells from 11- to 16-day-old rats. Under current clamp conditions, E-4031 enhanced hypoxia-induced depolarization in type I cells from 0- to- 1-day-old but not 11- to 16-day-old rats. With use of fura 2 to measure intracellular Ca2+, E-4031 increased the cytosolic Ca2+ concentration response to anoxia in cells from 0- to- 1-day-old but not cells from 11- to 16-day-old rats. E-4031-sensitive K+ currents are present in newborn carotid body type I cells and decline with age. These findings are consistent with a role for E-4031-sensitive K+ current, and possibly HERG-like K+ currents, in the type I cell hypoxia response maturation.

scholarly journals K2P2.1 (TREK-1) potassium channel activation protects against hyperoxia-induced lung injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tatiana Zyrianova ◽  
Benjamin Lopez ◽  
Riccardo Olcese ◽  
John Belperio ◽  
Christopher M. Waters ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Compliance ◽  
Alveolar Epithelial Cells ◽  
Pharmacological Intervention ◽  
Alveolar Epithelial ◽  
Protein Levels ◽  
Cell Counts ◽  
Novel Approach ◽  
Intracellular Ca ◽  
Cell Depolarization

AbstractNo targeted therapies exist to counteract Hyperoxia (HO)-induced Acute Lung Injury (HALI). We previously found that HO downregulates alveolar K2P2.1 (TREK-1) K+ channels, which results in worsening lung injury. This decrease in TREK-1 levels leaves a subset of channels amendable to pharmacological intervention. Therefore, we hypothesized that TREK-1 activation protects against HALI. We treated HO-exposed mice and primary alveolar epithelial cells (AECs) with the novel TREK-1 activators ML335 and BL1249, and quantified physiological, histological, and biochemical lung injury markers. We determined the effects of these drugs on epithelial TREK-1 currents, plasma membrane potential (Em), and intracellular Ca2+ (iCa) concentrations using fluorometric assays, and blocked voltage-gated Ca2+ channels (CaV) as a downstream mechanism of cytokine secretion. Once-daily, intra-tracheal injections of HO-exposed mice with ML335 or BL1249 improved lung compliance, histological lung injury scores, broncho-alveolar lavage protein levels and cell counts, and IL-6 and IP-10 concentrations. TREK-1 activation also decreased IL-6, IP-10, and CCL-2 secretion from primary AECs. Mechanistically, ML335 and BL1249 induced TREK-1 currents in AECs, counteracted HO-induced cell depolarization, and lowered iCa2+ concentrations. In addition, CCL-2 secretion was decreased after L-type CaV inhibition. Therefore, Em stabilization with TREK-1 activators may represent a novel approach to counteract HALI.

Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

2019 ◽  
Vol 13 (615) ◽  
pp. eaay9452 ◽  
Author(s):  
Alejandro Moreno-Domínguez ◽  
Patricia Ortega-Sáenz ◽  
Lin Gao ◽  
Olalla Colinas ◽  
Paula García-Flores ◽  
...  
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Acute Hypoxia ◽  
Mechanistic Explanation ◽  
Nerve Fibers ◽  
Adaptive Responses ◽  
Glomus Cells ◽  
Adult Mice ◽  
Genes Encoding ◽  
Regulation Of Breathing

Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.

scholarly journals Increase in cytosolic Ca2+produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body

2014 ◽  
Vol 592 (9) ◽  
pp. 1975-1992 ◽  
Author(s):  
Dawon Kang ◽  
Jiaju Wang ◽  
James O. Hogan ◽  
Rudi Vennekens ◽  
Marc Freichel ◽  
...  
Keyword(s):  
Carotid Body ◽  
Cation Channel ◽  
Chemoreceptor Cells

scholarly journals Human trabecular meshwork cell volume regulation

2002 ◽  
Vol 283 (1) ◽  
pp. C315-C326 ◽  
Author(s):  
Claire H. Mitchell ◽  
Johannes C. Fleischhauer ◽  
W. Daniel Stamer ◽  
K. Peterson-Yantorno ◽  
Mortimer M. Civan
Keyword(s):  
Cell Volume ◽  
Trabecular Meshwork ◽  
Regulatory Volume Decrease ◽  
Cell Volume Regulation ◽  
Channel Blockers ◽  
Uptake Mechanism ◽  
Fluid Uptake ◽  
Intracellular Ca ◽  
Predominant Effect ◽  
Volume Decrease

The volume of certain subpopulations of trabecular meshwork (TM) cells may modify outflow resistance of aqueous humor, thereby altering intraocular pressure. This study examines the contribution that Na+/H+, Cl−/HCO[Formula: see text]exchange, and K+-Cl− efflux mechanisms have on the volume of TM cells. Volume, Cl− currents, and intracellular Ca2+ activity of cultured human TM cells were studied with calcein fluorescence, whole cell patch clamping, and fura 2 fluorescence, respectively. At physiological bicarbonate concentration, the selective Na+/H+ antiport inhibitor dimethylamiloride reduced isotonic cell volume. Hypotonicity triggered a regulatory volume decrease (RVD), which could be inhibited by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), the K+channel blockers Ba2+ and tetraethylammonium, and the K+-Cl− symport blocker [(dihydroindenyl)oxy]alkanoic acid. The fluid uptake mechanism in isotonic conditions was dependent on bicarbonate; at physiological levels, the Na+/H+ exchange inhibitor dimethylamiloride reduced cell volume, whereas at low levels the Na+-K+-2Cl− symport inhibitor bumetanide had the predominant effect. Patch-clamp measurements showed that hypotonicity activated an outwardly rectifying, NPPB-sensitive Cl− channel displaying the permeability ranking Cl− > methylsulfonate > aspartate. 2,3-Butanedione 2-monoxime antagonized actomyosin activity and both increased baseline [Ca2+] and abolished swelling-activated increase in [Ca2+], but it did not affect RVD. Results indicate that human TM cells display a Ca2+-independent RVD and that volume is regulated by swelling-activated K+ and Cl− channels, Na+/H+ antiports, and possibly K+-Cl− symports in addition to Na+-K+-2Cl− symports.

scholarly journals Exposure to cyclic intermittent hypoxia increases expression of functional NMDA receptors in the rat carotid body

2009 ◽  
Vol 106 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Yuzhen Liu ◽  
En-Sheng Ji ◽  
Shuanglin Xiang ◽  
Renaud Tamisier ◽  
Jingli Tong ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Excitatory Neurotransmitter ◽  
Mk 801 ◽  
Baseline Activity ◽  
Nmda Receptor Blocker

Although large quantities of glutamate are found in the carotid body, to date this excitatory neurotransmitter has not been assigned a role in chemoreception. To examine the possibility that glutamate and its N-methyl-d-aspartate (NMDA) receptors play a role in acclimatization after exposure to cyclic intermittent hypoxia (CIH), we exposed male Sprague-Dawley rats to cyclic hypoxia or to room air sham (Sham) for 8 h/day for 3 wk. Using RT-PCR, Western blot analysis, and immunohistochemistry, we found that ionotropic NMDA receptors, including NMDAR1, NMDAR2A, NMDAR2A/2B, are strongly expressed in the carotid body and colocalize with tyrosine hydroxylase in glomus cells. CIH exposure enhanced the expression of NMDAR1 and NMDAR2A/2B but did not substantially change the level of NMDAR2A. We assessed in vivo carotid sinus nerve activity (CSNA) at baseline, in response to acute hypoxia, in response to infused NMDA, and in response to infused endothelin-1 (ET-1) with and without MK-801, an NMDA receptor blocker. Infusion of NMDA augmented CSNA in CIH rats (124.61 ± 2.64% of baseline) but not in sham-exposed rats. Administration of MK-801 did not alter baseline activity or response to acute hypoxia, in either CIH or sham animals but did reduce the effect of ET-1 infusion on CSNA (CSNA after ET-1 = 160.96 ± 8.05% of baseline; ET-1 after MK-801 = 118.56 ± 9.12%). We conclude that 3-wk CIH exposure increases expression of NMDA functional receptors in rats, suggesting glutamate and its receptors may play a role in hypoxic acclimatization to CIH.

Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels

2005 ◽  
Vol 289 (1) ◽  
pp. L5-L13 ◽  
Author(s):  
Letitia Weigand ◽  
Joshua Foxson ◽  
Jian Wang ◽  
Larissa A. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Cation Channels ◽  
Pulmonary Vasoconstriction ◽  
Nonselective Cation Channels ◽  
Pressor Responses ◽  
Intracellular Ca ◽  
Pulmonary Arterial

Previous studies indicated that acute hypoxia increased intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, and capacitative Ca2+ entry (CCE) through store-operated Ca2+ channels (SOCC) in smooth muscle cells from distal pulmonary arteries (PASMC), which are thought to be a major locus of hypoxic pulmonary vasoconstriction (HPV). Moreover, these effects were blocked by Ca2+-free conditions and antagonists of SOCC and nonselective cation channels (NSCC). To test the hypothesis that in vivo HPV requires CCE, we measured the effects of SOCC/NSCC antagonists (SKF-96365, NiCl2, and LaCl3) on pulmonary arterial pressor responses to 2% O2 and high-KCl concentrations in isolated rat lungs. At concentrations that blocked CCE and [Ca2+]i responses to hypoxia in PASMC, SKF-96365 and NiCl2 prevented and reversed HPV but did not alter pressor responses to KCl. At 10 μM, LaCl3 had similar effects, but higher concentrations (30 and 100 μM) caused vasoconstriction during normoxia and potentiated HPV, indicating actions other than SOCC blockade. Ca2+-free perfusate and the voltage-operated Ca2+ channel (VOCC) antagonist nifedipine were potent inhibitors of pressor responses to both hypoxia and KCl. We conclude that HPV required influx of Ca2+ through both SOCC and VOCC. This dual requirement and virtual abolition of HPV by either SOCC or VOCC antagonists suggests that neither channel provided enough Ca2+ on its own to trigger PASMC contraction and/or that during hypoxia, SOCC-dependent depolarization caused secondary activation of VOCC.

Sign in / Sign up

Export Citation Format

Share Document