Interactions between hypoxia and hypercapnic acidosis on calcium signaling in carotid body type I cells

2000 ◽  
Vol 279 (1) ◽  
pp. L36-L42 ◽  
Author(s):  
Leonardo L. T. Dasso ◽  
Keith J. Buckler ◽  
Richard D. Vaughan-Jones
Keyword(s):  
Carotid Body ◽  
Neonatal Rat ◽  
Single Type ◽  
Type I ◽  
Hypercapnic Acidosis ◽  
Body Type ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
I Cells

The effects of hypercapnic acidosis and hypoxia on intracellular Ca2+concentration ([Ca2+]i) were determined with Indo 1 in enzymatically isolated single type I cells from neonatal rat carotid bodies. Type I cells responded to graded hypoxic stimuli with graded [Ca2+]i rises. The percentage of cells responding was also dependent on the severity of the hypoxic stimulus. Raising CO2 from 5 to 10 or 20% elicited a significant increase in [Ca2+]i in the same cells as those that responded to hypoxia. Thus both stimuli can be sensed by each individual cell. When combinations of hypoxic and acidic stimuli were given simultaneously, the responses were invariably greater than the response to either stimulus given alone. Indeed, in most cases, the response to hypercapnia was slightly potentiated by hypoxia. These data provide the first evidence that the classic synergy between hypoxic and hypercapnic stimuli observed in the intact carotid body may, in part, be an inherent property of the type I cell.

scholarly journals Gene expression and function of adenosine A2A receptor in the rat carotid body

2000 ◽  
Vol 279 (2) ◽  
pp. L273-L282 ◽  
Author(s):  
Shuichi Kobayashi ◽  
Laura Conforti ◽  
David E. Millhorn
Keyword(s):  
Carotid Body ◽  
Cellular Response ◽  
Cell Voltage ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
Immunohistochemical Studies ◽  
I Cells ◽  
Receptor Mrnas

The present study was undertaken to determine whether rat carotid bodies express adenosine (Ado) A2A receptors and whether this receptor is involved in the cellular response to hypoxia. Our results demonstrate that rat carotid bodies express the A2A and A2B Ado receptor mRNAs but not the A1 or A3 receptor mRNAs as determined by reverse transcriptase-polymerase chain reaction. In situ hybridization confirmed the expression of the A2A receptor mRNA. Immunohistochemical studies further showed that the A2A receptor is expressed in the carotid body and that it is colocalized with tyrosine hydroxylase in type I cells. Whole cell voltage-clamp studies using isolated type I cells showed that Ado inhibited the voltage-dependent Ca2+ currents and that this inhibition was abolished by the selective A2A receptor antagonist ZM-241385. Ca2+ imaging studies using fura 2 revealed that exposure to severe hypoxia induced elevation of intracellular Ca2+ concentration ([Ca2+]i) in type I cells and that extracellularly applied Ado significantly attenuated the hypoxia-induced elevation of [Ca2+]i. Taken together, our findings indicate that A2A receptors are present in type I cells and that activation of A2Areceptors modulates Ca2+ accumulation during hypoxia. This mechanism may play a role in regulating intracellular Ca2+homeostasis and cellular excitability during hypoxia.

scholarly journals Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine

2009 ◽  
Vol 168 (3) ◽  
pp. 218-223 ◽  
Author(s):  
Drew C. Burlon ◽  
Heidi L. Jordan ◽  
Christopher N. Wyatt
Keyword(s):  
Carotid Body ◽  
Neonatal Rat ◽  
Type I ◽  
Body Type ◽  
Type I Cells ◽  
Presynaptic Regulation ◽  
I Cells

Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body

1995 ◽  
Vol 78 (5) ◽  
pp. 1904-1909 ◽  
Author(s):  
W. Kummer ◽  
H. Acker
Keyword(s):  
Hydrogen Peroxide ◽  
Carotid Body ◽  
Oxygen Sensor ◽  
Neutrophil Granulocytes ◽  
Type I ◽  
Body Type ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Sensor Protein ◽  
I Cells

We demonstrate, by means of immunohistochemistry, that type I cells of human, guinea pig, and rat carotid bodies react with antisera raised against the subunits p22phox, gp91phox, p47phox, and p67phox of the NAD(P)H oxidase isolated from human neutrophil granulocytes. The findings support previous photometric studies that indicate that carotid body type I cells possess a putative oxygen sensor protein that is similar to the neutrophil NAD(P)H oxidase and consists of a hydrogen peroxide generating low-potential cytochrome b558 with cofactors regulating the electron transfer to oxygen.

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.

Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice

2002 ◽  
Vol 282 (1) ◽  
pp. C27-C33 ◽  
Author(s):  
L. He ◽  
J. Chen ◽  
B. Dinger ◽  
K. Sanders ◽  
K. Sundar ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Nadph Oxidase ◽  
Carotid Body ◽  
Gene Knockout ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
Marker Antigen ◽  
I Cells

Various heme-containing proteins have been proposed as primary molecular O2 sensors for hypoxia-sensitive type I cells in the mammalian carotid body. One set of data in particular supports the involvement of a cytochrome b NADPH oxidase that is commonly found in neutrophils. Subunits of this enzyme have been immunocytochemically localized in type I cells, and diphenyleneiodonium, an inhibitor of the oxidase, increases carotid body chemoreceptor activity. The present study evaluated immunocytochemical and functional properties of carotid bodies from normal mice and from mice with a disrupted gp91 phagocytic oxidase (gp91 phox ) DNA sequence gene knockout (KO), a gene that codes for a subunit of the neutrophilic form of NADPH oxidase. Immunostaining for tyrosine hydroxylase, a signature marker antigen for type I cells, was found in groups or lobules of cells displaying morphological features typical of the O2-sensitive cells in other species, and the incidence of tyrosine hydroxylase-immunopositive cells was similar in carotid bodies from both strains of mice. Studies of whole cell K+currents also revealed identical current-voltage relationships and current depression by hypoxia in type I cells dissociated from normal vs. KO animals. Likewise, hypoxia-evoked increases in intracellular Ca2+ concentration were not significantly different for normal and KO type I cells. The whole organ response to hypoxia was evaluated in recordings of carotid sinus nerve activity in vitro. In these experiments, responses elicited by hypoxia and by the classic chemoreceptor stimulant nicotine were also indistinguishable in normal vs. KO preparations. Our data demonstrate that carotid body function remains intact after sequence disruption of the gp91 phox gene. These findings are not in accord with the hypothesis that the phagocytic form of NADPH oxidase acts as a primary O2 sensor in arterial chemoreception.

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