scholarly journals Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide

2004 ◽  
Vol 555 (1) ◽  
pp. 219-229 ◽  
Author(s):  
Yu-Long Li ◽  
Shu-Yu Sun ◽  
Jeffery L. Overholt ◽  
Nanduri R. Prabhakar ◽  
George J. Rozanski ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Carotid Body ◽  
Potassium Currents ◽  
Glomus Cells ◽  
Carotid Body Glomus Cells

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.

scholarly journals Nitric Oxide Inhibits L-Type Ca2+ Current in Glomus Cells of the Rabbit Carotid Body Via a cGMP-Independent Mechanism

1999 ◽  
Vol 81 (4) ◽  
pp. 1449-1457 ◽  
Author(s):  
Beth A. Summers ◽  
Jeffrey L. Overholt ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nitric Oxide ◽  
Carotid Body ◽  
Channel Blocker ◽  
Adult Rabbit ◽  
Subsequent Formation ◽  
No Donors ◽  
Glomus Cells ◽  
Channel Proteins ◽  
Carotid Bodies ◽  
Independent Mechanism

Nitric oxide inhibits L-type Ca2+ current in glomus cells of the rabbit carotid body via a cGMP-independent mechanism. Previous studies have shown that nitric oxide (NO) inhibits carotid body sensory activity. To begin to understand the cellular mechanisms associated with the actions of NO in the carotid body, we monitored the effects of NO donors on the macroscopic Ca2+ current in glomus cells isolated from rabbit carotid bodies. Experiments were performed on freshly dissociated glomus cells from adult rabbit carotid bodies using the whole cell configuration of the patch-clamp technique. The NO donors sodium nitroprusside (SNP; 600 μM, n = 7) and spermine nitric oxide (SNO; 100 μM, n = 7) inhibited the Ca2+ current in glomus cells in a voltage-independent manner. These effects of NO donors were rapid in onset and peaked within 1 or 2 min. In contrast, the outward K+ current was unaffected by SNP (600 μM, n = 6), indicating that the inhibition by SNP was not a nonspecific membrane effect. 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (carboxy-PTIO; 500 μM), an NO scavenger, prevented inhibition of the Ca2+ current by SNP ( n = 7), whereas neither superoxide dismutase (SOD; 2,000 U/ml, n = 4), a superoxide scavenger, nor sodium hydrosulfite (SHS; 1 mM, n = 7), a reducing agent, prevented inhibition of the Ca2+ current by SNP. However, SNP inhibition of the Ca2+ current was reversible in the presence of either SOD or SHS. These results suggest that NO itself inhibits Ca2+current in a reversible manner and that subsequent formation of peroxynitrites results in irreversible inhibition. SNP inhibition of the Ca2+ current was not affected by 30 μM LY 83,583 ( n = 7) nor was it mimicked by 600 μM 8-bromoguanosine 3′:5′-cyclic monophosphate (8-Br-cGMP; n = 6), suggesting that the effects of NO on the Ca2+ current are mediated, in part, via a cGMP-independent mechanism. N-ethylmaleimide (NEM; 2.5 mM, n= 6) prevented the inhibition of the Ca2+ current by SNP, indicating that SNP is acting via a modification of sulfhydryl groups on Ca2+ channel proteins. Norepinephrine (NE; 10 μM) further inhibited the Ca2+ current in the presence of NEM ( n = 7), implying that NEM did not nonspecifically eliminate Ca2+ current modulation. Nisoldipine, an L-type Ca2+ channel blocker (2 μM, n = 6), prevented the inhibition of Ca2+ current by SNP, whereas ω-conotoxin GVIA, an N-type Ca2+ channel blocker (1 μM, n = 9), did not prevent the inhibition of Ca2+ current by SNP. These results demonstrate that NO inhibits L-type Ca2+ channels in adult rabbit glomus cells, in part, due to a modification of calcium channel proteins. The inhibition might provide one plausible mechanism for efferent inhibition of carotid body activity by NO.

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

Norepinephrine Inhibits a Toxin Resistant Ca2+ Current in Carotid Body Glomus Cells: Evidence for a Direct G Protein Mechanism

1999 ◽  
Vol 81 (1) ◽  
pp. 225-233 ◽  
Author(s):  
Jeffrey L. Overholt ◽  
Nanduri R. Prabhakar
Keyword(s):  
Receptor Antagonist ◽  
G Protein ◽  
G Proteins ◽  
Carotid Body ◽  
Adrenergic Receptor ◽  
Subunit Interaction ◽  
Whole Cell ◽  
Glomus Cells ◽  
Voltage Dependent ◽  
Carotid Body Glomus Cells

Overholt, Jeffrey L. and Nanduri R. Prabhakar. Norepinephrine inhibits a toxin resistant Ca2+ current in carotid body glomus cells: evidence for a direct G protein mechanism. J. Neurophysiol. 81: 225–233, 1999. Previous studies have demonstrated that endogenous norepinephrine (NE) inhibits carotid body (CB) sensory discharge, and the cellular actions of NE have been associated with inhibition of Ca2+ current in glomus cells. The purpose of the present study was to elucidate the characteristics and mechanism of NE inhibition of whole cell Ca2+ current isolated from rabbit CB glomus cells and to determine the type(s) of Ca2+ channel involved. NE (10 μM) inhibited 24 ± 2% (SE) of the macroscopic Ca2+ current measured at the end of a 25 ms pulse to 0 mV and slowed activation of the current. The α2 adrenergic receptor antagonist, SK&F 86466, attenuated these effects. Inhibition by NE was fast and voltage-dependent i.e., maximal at −10 mV and then diminished with stronger depolarizations. This is characteristic of G protein βγ subunit interaction with the α1 subunit of certain Ca2+ channels, which can be relieved by depolarizing steps. A depolarizing step (30 ms to +80 mV) significantly increased (14 ± 1%) current in the presence of NE, whereas it had no effect before application of NE (1 ± 1%). To further test for the involvement of G proteins, NE was applied to cells where intracellular GTP was replaced by GDP-βS. NE had little or no effect on Ca2+ current in cells dialyzed with GDP-βS. To determine whether NE was inhibiting N- and/or P/Q-type channels, we applied NE in the presence of ω-conotoxin MVIIC (MVIIC). In the presence of 2.5 μM MVIIC, NE was equally potent at inhibiting the Ca2+ current (23 ± 4% vs. 23 ± 4% in control), suggesting that NE was not exclusively inhibiting N- or P/Q-type channels. NE was also equally potent (30 ± 2% vs. 26 ± 4% in control) at inhibiting the Ca2+ current in the presence of 2 μM nisoldipine, suggesting that NE was not inhibiting L-type channels. Further, NE inhibited a significantly larger proportion (47 ± 6%) of the resistant Ca2+ current remaining in the presence of NISO and MVIIC. These results suggest that NE inhibition of Ca2+ current in rabbit CB glomus cells is mediated in most part by effects on the resistant, non L-, N-, or P/Q-type channel and involves a direct G protein βγ interaction with this channel.

scholarly journals Perinatal hyperoxia exposure impairs hypoxia-induced depolarization in rat carotid body glomus cells

2013 ◽  
Vol 188 (1) ◽  
pp. 9-14 ◽  
Author(s):  
Insook Kim ◽  
Dongjin Yang ◽  
John L. Carroll ◽  
David F. Donnelly
Keyword(s):  
Carotid Body ◽  
Glomus Cells ◽  
Hyperoxia Exposure ◽  
Carotid Body Glomus Cells
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