scholarly journals Acid-Sensing Ion Channels Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells

2007 ◽  
Vol 101 (10) ◽  
pp. 1009-1019 ◽  
Author(s):  
Zhi-Yong Tan ◽  
Yongjun Lu ◽  
Carol A. Whiteis ◽  
Christopher J. Benson ◽  
Mark W. Chapleau ◽  
...  
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Glomus Cells ◽  
Extracellular Acidosis ◽  
Acid Sensing Ion Channels ◽  
Carotid Body Glomus Cells

Abstract 956: Acid-Sensing Ion Channels (ASICs) Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Zhi-Yong Tan ◽  
Yongjun Lu ◽  
Carol A Whiteis ◽  
Christopher J Benson ◽  
Mark W Chapleau ◽  
...  
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Bathing Solution ◽  
Ph Sensing ◽  
Pipette Solution ◽  
Glomus Cells ◽  
Extracellular Acidosis ◽  
Task Channels ◽  
Carotid Body Chemoreceptors ◽  
Carotid Body Glomus Cells

The molecular mechanism of pH sensing by chemoreceptors is not clear, although it had been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K + current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH-sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward currents in glomus cells that were evident at pH 7.0 and half-activated (pH 50) at 6.3. The current had the characteristics of ASICs. It averaged 40.7±15.7 pA (n=5) at pH 5.0 and was blocked by the ASIC channel blocker amiloride (200 μm) to 2.5±1.6 pA. Na + free bathing solution eliminated the current and a Ca 2+ free buffer enhanced (P<0.05) the current at pH 6.0 from 18.5±2.2 to 86.0±12.5 pA (n=5). Enhancement of the current was also seen with the addition of lactate. In the current clamp mode extracellular acidosis evoked both a transient and sustained depolarization. The initial transient component at pH 6.0 averaged 18.2±2.6 mV and was blocked by amiloride to 2.1±2.1 mV supporting the contribution of ASICs. However, the sustained depolarization was not blocked by amiloride but was eliminated by removal of K + from the pipette solution which reduced significantly intracellular K + . This sustained depolarization was partially blocked by the TASK channels blockers anandamide (from 14.9±1.6 mV to 9.3±2.2 mV at pH 6.0, n=5) and quinidine (from 27.5±2.2 mV to 11.3±2.3 mV at pH 6.0, n=3). The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors, and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels.

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 Endogenous H2S is required for hypoxic sensing by carotid body glomus cells

2012 ◽  
Vol 303 (9) ◽  
pp. C916-C923 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Jayasri Nanduri ◽  
Gayatri Raghuraman ◽  
Aaron P. Fox ◽  
Moataz M. Gadalla ◽  
...  
Keyword(s):  
Carotid Body ◽  
Time Course ◽  
Channel Blocker ◽  
Primary Site ◽  
Dependent Manner ◽  
Free Medium ◽  
Adult Rats ◽  
Glomus Cells ◽  
Dose Dependent ◽  
Carotid Body Glomus Cells

H2S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O2 sensing by the carotid body. The objectives of the present study were to determine whether glomus cells, the primary site of hypoxic sensing in the carotid body, generate H2S in an O2-sensitive manner and whether endogenous H2S is required for O2 sensing by glomus cells. Experiments were performed on glomus cells harvested from anesthetized adult rats as well as age and sex-matched CSE+/+ and CSE−/− mice. Physiological levels of hypoxia (Po2 ∼30 mmHg) increased H2S levels in glomus cells, and dl-propargylglycine (PAG), a CSE inhibitor, prevented this response in a dose-dependent manner. Catecholamine (CA) secretion from glomus cells was monitored by carbon-fiber amperometry. Hypoxia increased CA secretion from rat and mouse glomus cells, and this response was markedly attenuated by PAG and in cells from CSE−/− mice. CA secretion evoked by 40 mM KCl, however, was unaffected by PAG or CSE deletion. Exogenous application of a H2S donor (50 μM NaHS) increased cytosolic Ca2+ concentration ([Ca2+]i) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca2+]i responses to NaHS and hypoxia were markedly attenuated in the presence of Ca2+-free medium or cadmium chloride, a pan voltage-gated Ca2+ channel blocker, or nifedipine, an L-type Ca2+ channel inhibitor, suggesting that both hypoxia and H2S share common Ca2+-activating mechanisms. These results demonstrate that H2S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.

Ca2+ Current in Rabbit Carotid Body Glomus Cells Is Conducted by Multiple Types of High-Voltage–Activated Ca2+ Channels

1997 ◽  
Vol 78 (5) ◽  
pp. 2467-2474 ◽  
Author(s):  
Jeffrey L. Overholt ◽  
Nanduri R. Prabhakar
Keyword(s):  
High Voltage ◽  
Carotid Body ◽  
Neurotransmitter Release ◽  
Relative Proportion ◽  
Sensory Transduction ◽  
Arterial Oxygen ◽  
Patch Clamp Technique ◽  
Simultaneous Application ◽  
Glomus Cells ◽  
Carotid Body Glomus Cells

Overholt, Jeffrey L. and Nanduri R. Prabhakar. Ca2+ current in rabbit carotid body glomus cells is conducted by multiple types of high-voltage–activated Ca2+ channels. J. Neurophysiol. 78: 2467–2474, 1997. Carotid bodies are sensory organs that detect changes in arterial oxygen. Glomus cells are presumed to be the initial sites for sensory transduction, and Ca2+-dependent neurotransmitter release from glomus cells is believed to be an obligatory step in this response. Some information exists on the Ca2+ channels in rat glomus cells. However, relatively little is known about the types of Ca2+ channels present in rabbit glomus cells, the species in which most of the neurotransmitter release studies have been performed. Therefore we tested the effect of specific Ca2+ channel blockers on current recorded from freshly dissociated, adult rabbit carotid body glomus cells using the whole cell configuration of the patch-clamp technique. Macroscopic Ba2+ current elicited from a holding potential of −80 mV activated at a V m of approximaely −30 mV, peaked between 0 and +10 mV and did not inactivate during 25-ms steps to positive test potentials. Prolonged (≈2 min) depolarized holding potentials inactivated the current with a V 1/2 of −47 mV. There was no evidence for T-type channels. On steps to 0 mV, 6 mM Co2+ decreased peak inward current by 97 ± 1% (mean ± SE). Nisoldipine (2 μM), 1 μM ω-conotoxin GVIA, and 100 nM ω-agatoxin IVa each blocked a portion of the macroscopic Ca2+ current (30 ± 5, 33 ± 5, and 19 ± 3% after rundown correction, respectively). Simultaneous application of these blockers revealed a resistant current that was not affected by 1 μMω-conotoxin MVIIC. This resistant current constituted 27 ± 5% of the total macroscopic Ca2+ current. Each blocker had an effect in every cell so tested. However, the relative proportion of current blocked varied from cell to cell. These results suggest that L, N, P, and resistant channel types each conduct a significant proportion of the macroscopic Ca2+ current in rabbit glomus cells. Hypoxia-induced neurotransmitter release from glomus cells may involve one or more of these channels.

scholarly journals Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells.

1994 ◽  
Vol 91 (21) ◽  
pp. 10208-10211 ◽  
Author(s):  
J. Urena ◽  
R. Fernandez-Chacon ◽  
A. R. Benot ◽  
G. A. Alvarez de Toledo ◽  
J. Lopez-Barneo
Keyword(s):  
Carotid Body ◽  
Glomus Cells ◽  
Voltage Dependent ◽  
Carotid Body Glomus Cells
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