scholarly journals Roles of Ion Channels in Carotid Body Chemotransmission of Acute Hypoxia.

1999 ◽  
Vol 49 (3) ◽  
pp. 213-228 ◽  
Author(s):  
Machiko SHIRAHATA ◽  
James S.K. SHAM
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Acute Hypoxia

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 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.

Chronic phenytoin treatment reduces rat carotid body chemosensory responses to acute hypoxia

2016 ◽  
Vol 1649 ◽  
pp. 38-43
Author(s):  
Julio Alcayaga ◽  
María P. Oyarce ◽  
Rodrigo Del Rio
Keyword(s):  
Carotid Body ◽  
Acute Hypoxia

scholarly journals Gasotransmitter Regulation of Ion Channels: A Key Step in O2 Sensing By the Carotid Body

Physiology ◽  
2014 ◽  
Vol 29 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Chris Peers
Keyword(s):  
Ion Channels ◽  
Carotid Body ◽  
Physiological Responses ◽  
Current Understanding ◽  
Body Function ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Review Current ◽  
O2 Sensing

Carotid bodies detect hypoxia in arterial blood, translating this stimulus into physiological responses via the CNS. It is long established that ion channels are critical to this process. More recent evidence indicates that gasotransmitters exert powerful influences on O2 sensing by the carotid body. Here, we review current understanding of hypoxia-dependent production of gasotransmitters, how they regulate ion channels in the carotid body, and how this impacts carotid body function.

scholarly journals Effect of hyperoxic exposure during early development on neurotrophin expression in the carotid body and nucleus tractus solitarii

2012 ◽  
Vol 112 (10) ◽  
pp. 1762-1772 ◽  
Author(s):  
Raul Chavez-Valdez ◽  
Ariel Mason ◽  
Ana R. Nunes ◽  
Frances J. Northington ◽  
Clarke Tankersley ◽  
...  
Keyword(s):  
Protein Expression ◽  
Carotid Body ◽  
Acute Hypoxia ◽  
Synaptic Activity ◽  
Nucleus Tractus Solitarii ◽  
Mrna Levels ◽  
Bdnf Mrna ◽  
Rat Pups ◽  
Hyperoxic Exposure ◽  
And Shifts

Synaptic activity can modify expression of neurotrophins, which influence the development of neuronal circuits. In the newborn rat, early hyperoxia silences the synaptic activity and input from the carotid body, impairing the development and function of chemoreceptors. The purpose of this study was to determine whether early hyperoxic exposure, sufficient to induce hypoplasia of the carotid body and decrease the number of chemoafferents, would also modify neurotrophin expression within the nucleus tractus solitarii (nTS). Rat pups were exposed to hyperoxia (fraction of inspired oxygen 0.60) or normoxia until 7 or 14 days of postnatal development (PND). In the carotid body, hyperoxia decreased brain-derived neurotrophic factor (BDNF) protein expression by 93% ( P = 0.04) after a 7-day exposure, followed by a decrease in retrogradely labeled chemoafferents by 55% ( P = 0.004) within the petrosal ganglion at 14 days. Return to normoxia for 1 wk after a 14-day hyperoxic exposure did not reverse this effect. In the nTS, hyperoxia for 7 days: 1) decreased BDNF gene expression by 67% and protein expression by 18%; 2) attenuated upregulation of BDNF mRNA levels in response to acute hypoxia; and 3) upregulated p75 neurotrophic receptor, truncated tropomyosin kinase B (inactive receptor), and cleaved caspase-3. These effects were not observed in the locus coeruleus (LC). Hyperoxia for 14 days also decreased tyrosine hydroxylase levels by 18% ( P = 0.04) in nTS but not in the LC. In conclusion, hyperoxic exposure during early PND reduces neurotrophin levels in the carotid body and the nTS and shifts the balance of neurotrophic support from prosurvival to proapoptotic in the nTS, the primary brain stem site for central integration of sensory and autonomic inputs.

scholarly journals Metabotropic Glutamate Receptors 1 Regulates Rat Carotid Body Response to Acute Hypoxia via Presynaptic Mechanism

2021 ◽  
Vol 15 ◽  
Author(s):  
Chaohong Li ◽  
Baosheng Zhao ◽  
Chenlu Zhao ◽  
Lu Huang ◽  
Yuzhen Liu
Keyword(s):  
Glutamate Receptors ◽  
Carotid Body ◽  
Cellular Localization ◽  
Metabotropic Glutamate Receptors ◽  
Physiological Function ◽  
Acute Hypoxia ◽  
Critical Role ◽  
Type I ◽  
Metabotropic Glutamate ◽  
Group I

Background: The carotid body (CB) plays a critical role in oxygen sensing; however, the role of glutamatergic signaling in the CB response to hypoxia remains uncertain. We previously found that functional multiple glutamate transporters and inotropic glutamate receptors (iGluRs) are expressed in the CB. The aim of this present research is to investigate the expression of group I metabotropic glutamate receptors (mGluRs) (mGluR1 and 5) in the CB and its physiological function in rat CB response to acute hypoxia.Methods: RT-PCR and immunostaining were conducted to examine the mRNA and protein expression of group I mGluRs in the human and rat CB. Immunofluorescence staining was performed to examine the cellular localization of mGluR1 in the rat CB. In vitro carotid sinus nerve (CSN) discharge recording was performed to detect the physiological function of mGluR1 in CB response to acute hypoxia.Results: We found that (1) mRNAs of mGluR1 and 5 were both expressed in the human and rat CB. (2) mGluR1 protein rather than mGluR5 protein was present in rat CB. (3) mGluR1 was distributed in type I cells of rat CB. (4) Activation of mGluR1 inhibited the hypoxia-induced enhancement of CSN activity (CSNA), as well as prolonged the latency time of CB response to hypoxia. (5) The inhibitory effect of mGluR1 activation on rat CB response to hypoxia could be blocked by GABAB receptor antagonist.Conclusion: Our findings reveal that mGluR1 in CB plays a presynaptic feedback inhibition on rat CB response to hypoxia.

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.

Sign in / Sign up

Export Citation Format

Share Document