Activation of the release of dopamine in the carotid body by veratridine. Evidence for the presence of voltage-dependent Na+ channels in type I cells

1988 ◽  
Vol 94 (3) ◽  
pp. 274-278 ◽  
Author(s):  
Asunción Rocher ◽  
Ana Obeso ◽  
Benito Herreros ◽  
Constancio Gonzalez
Keyword(s):  
Carotid Body ◽  
Type I ◽  
Na Channels ◽  
Type I Cells ◽  
Voltage Dependent ◽  
I Cells

L-type calcium channels in type I cells of the rat carotid body

1993 ◽  
Vol 70 (4) ◽  
pp. 1378-1384 ◽  
Author(s):  
L. A. Fieber ◽  
E. W. McCleskey
Keyword(s):  
Carotid Body ◽  
Single Channel ◽  
Bay K 8644 ◽  
Type I ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Type I Cells ◽  
Voltage Dependent ◽  
I Cells ◽  
Ca2 Channels

1. Whole-cell and cell-attached patch-clamp recordings were made from enzymatically isolated type I cells from the carotid body of adult rats. Voltage-dependent K+ and Ca2+ channels were observed, but there was no detectable Na+ current. In this respect, rat carotid body cells are unlike those from rabbit, which have Na+ currents and Na(+)-dependent action potentials. 2. The observed Ca2+ channels had the following properties: 1) activation requires voltage steps above -20 mV; 2) little inactivation occurred with holding voltages below -40 mV; 3) one single-channel conductance of 21 pS was found with 90 or 110 mM Ba2+ in the cell-attached pipette and this was the only conductance observed; 4) open probability was increased by the dihydropyridine Ca2+ channel agonist Bay K 8644 and was decreased by the antagonist nifedipine; and 5) omega-conotoxin had little or no effect on the channels. These are properties expected of L-type Ca2+ channels. 3. To investigate whether these voltage-dependent channels would be available for opening on membrane depolarization, we measured the type I cell resting membrane potential noninvasively using unitary openings of the L-type Ca2+ channel with Bay K 8644 in the cell-attached pipette. Resting potentials ranged from -62 to -13 mV, with a mean of -32 mV in 12 cells. 4. Judging from single-channel conductance and pharmacology, the Ca2+ current is mostly, if not solely, carried by L channels. Thus it should be possible to use modulators of L channel activity to determine the role of Ca2+ channels in stimulus-secretion coupling in the rat carotid body.

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.

scholarly journals Immunohistochemical Characteristics of the Human Carotid Body in the Antenatal and Postnatal Periods of Development

2021 ◽  
Vol 22 (15) ◽  
pp. 8222
Author(s):  
Dmitry Otlyga ◽  
Ekaterina Tsvetkova ◽  
Olga Junemann ◽  
Sergey Saveliev
Keyword(s):  
Tyrosine Hydroxylase ◽  
Carotid Body ◽  
Nerve Fibers ◽  
Individual Development ◽  
Endocrine Function ◽  
Type I ◽  
Type I Cells ◽  
Carotid Bodies ◽  
I Cells ◽  
Human Carotid

The evolutionary and ontogenetic development of the carotid body is still understudied. Research aimed at studying the comparative morphology of the organ at different periods in the individual development of various animal species should play a crucial role in understanding the physiology of the carotid body. However, despite more than two centuries of study, the human carotid body remains poorly understood. There are many knowledge gaps in particular related to the antenatal development of this structure. The aim of our work is to study the morphological and immunohistochemical characteristics of the human carotid body in the antenatal and postnatal periods of development. We investigated the human carotid bodies from 1 embryo, 20 fetuses and 13 adults of different ages using samples obtained at autopsy. Immunohistochemistry revealed expression of βIII-tubulin and tyrosine hydroxylase in the type I cells and nerve fibers at all periods of ontogenesis; synaptophysin and PGP9.5 in the type I cells in some of the antenatal cases and all of the postnatal cases; 200 kDa neurofilaments in nerve fibers in some of the antenatal cases and all of the postnatal cases; and GFAP and S100 in the type II cells and Schwann cells in some of the antenatal cases and all of the postnatal cases. A high level of tyrosine hydroxylase in the type I cells was a distinctive feature of the antenatal carotid bodies. On the contrary, in the type I cells of adults, the expression of tyrosine hydroxylase was significantly lower. Our data suggest that the human carotid body may perform an endocrine function in the antenatal period, while in the postnatal period of development, it loses this function and becomes a chemosensory organ.

Carotid Body Chemoreceptors: Physiology, Pathology, and Implications for Health and Disease

2021 ◽  
Author(s):  
Rodrigo Iturriaga ◽  
Julio Alcayaga ◽  
Mark W. Chapleau ◽  
Virend K Somers
Keyword(s):  
Carotid Body ◽  
Metabolic Diseases ◽  
Ionic Channels ◽  
Type I ◽  
Peripheral Chemoreceptor ◽  
Type I Cells ◽  
Obstructive Sleep ◽  
Carotid Body Chemoreceptors ◽  
Respiratory Gases ◽  
I Cells

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2, and pH, eliciting reflex ventilatory, cardiovascular and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiologic responses, and its role in maintaining health and potentiating disease. Emphasis will be placed on: i) Transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ionic channels; ii) Synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; iii) Integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and iv) The contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension and metabolic diseases, and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

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.

Effects of cytochrome P-450 inhibitors on ionic currents in isolated rat type I carotid body cells

1996 ◽  
Vol 271 (1) ◽  
pp. C85-C92 ◽  
Author(s):  
C. J. Hatton ◽  
C. Peers
Keyword(s):  
Carotid Body ◽  
Single Channel ◽  
Ionic Currents ◽  
K Channel ◽  
Type I ◽  
Type I Cells ◽  
Channel Inhibition ◽  
Cytochrome P 450 ◽  
I Cells ◽  
K Currents

Hypoxic chemoreception in the carotid body involves selective inhibition of K+ channels in type I cells. We have investigated whether cytochrome P-450 may act as an O2 sensor coupling hypoxia to K+ channel inhibition, by investigating the actions of P-450 inhibitors to modulate channel activity (recorded using patch-clamp techniques) in type I cells isolated from 8-to 12-day-old rat pups. The imidazole antimycotic P-450 inhibitors miconazole and clotrimazole (1-10 microM) inhibited the Ca(2+)-activated (KCa) and voltage-gated K+ (Kv) currents in isolated type I cells. Single-channel recordings indicated that the KCa channels could be inhibited directly by miconazole. Miconazole also irreversibly inhibited Ca2+ channel currents. By contrast, acute application of the suicide substrate P-450 inhibitor, 1-aminobenzotriazole (1-ABT; 3 mM) was without effect on K+ or Ca2+ currents. Hypoxia (16-23 mmHg) reversibly inhibited K+ currents and prevented the inhibitory actions of miconazole. Furthermore, the inhibitory actions of miconazole could be partially reversed by hypoxia. Pretreatment of cells for 60 min with 3 mM 1-ABT substantially reduced the inhibitory actions of hypoxia on K+ currents. Our results indicate that imidazole antimycotic P-450 inhibitors can directly and nonselectively inhibit ionic channels in type I cells but, more importantly, provide evidence to suggest that hypoxic inhibition of K+ currents in type I cells is mediated in part at least by cytochrome P-450.

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