Ionic mechanisms for the transduction of acidic stimuli in rabbit carotid body glomus cells.

Rocher, A.; Obeso, Ana; González, C.; Herreros, Benito

doi:10.1113/jphysiol.1991.sp018442

Cited by 68 publications

(61 citation statements)

References 36 publications

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“…We propose that, as for acidic and hypoxic stimuli, this [Ca¥]é response is a fundamental part of the chemotransduction process serving as the signal which evokes neurosecretion. This is supported by the observations that both the [Ca¥]é response and DNP-evoked neurosecretion are inhibited by the removal of extracellular calcium (Rocher et al 1991). It is apparent that the uncoupler-induced rise in [Ca¥]é is dependent upon cell membrane depolarization (Fig.…”

Section: Discussion Effects Of Uncouplers On [Ca¥]é Regulationsupporting

confidence: 73%

“…Figure 3A shows that replacing Naº with NMDG caused a substantial inhibition of the [Ca¥]é response to DNP (Ä[Ca¥]é (control vs. Na¤-free conditions): 447 ± 71 vs. 58 ± 14 nÒ, n = 4, P < 0·05). These data are consistent with the rise in [Ca¥]é being due to reverse mode Na¤-Ca¥ exchange (Rocher et al 1991). We have, however, previously reported that Na¤-free conditions inhibit the [Ca¥]é response to physiological acidic stimuli via an alternative mechanism.…”

Section: Cause Of Uncoupler-induced Rise In [Ca¥]ésupporting

confidence: 80%

“…The hypothesis that DNP acts as a strong acidic stimulus (Rocher et al 1991;Gonzalez et al 1994) was not supported by our data. Firstly DNP was found to produce only a weak intracellular acidification, secondly the [Ca¥]é responses observed were disproportionate to the strength of the acidic (pHé) stimulus, and thirdly alkalinizing the cell did not significantly inhibit the [Ca¥]é response to DNP.…”

Section: Effect Of Uncouplers Upon Phécontrasting

confidence: 55%

“…Na¤-H¤ exchange), and a rise in [Na¤]é. Indeed, it has been shown that the secretory response to DNP is inhibited in the absence of extracellular Na¤ (Rocher et al 1991). We therefore, tested the effects of sodium removal upon the [Ca¥]é response to DNP.…”

Section: Cause Of Uncoupler-induced Rise In [Ca¥]émentioning

confidence: 99%

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Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells

Buckler

Vaughan‐Jones

1998

The Journal of Physiology

171

120

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Mitochondrial uncouplers are potent stimulants of the carotid body. We have therefore investigated their effects upon isolated type I cells. Both 2,4‐dinitrophenol (DNP) and carbonyl cyanide p‐trifluoromethoxyphenyl hydrazone (FCCP) caused an increase in [Ca2+]i which was largely inhibited by removal of extracellular Ca2+ or Na+, or by the addition of 2 mm Ni2+. Methoxyverapamil (D600) also partially inhibited the [Ca2+]i response. In perforated‐patch recordings, the rise in [Ca2+]i coincided with membrane depolarization and was greatly reduced by voltage clamping the cell to −70 mV. Uncouplers also inhibited a background K+ current and induced a small inward current. Uncouplers reduced pHi by 0.1 unit. Alkaline media diminished this acidification but had no effect on the [Ca2+]i response. FCCP and DNP also depolarized type I cell mitochondria. The onset of mitochondrial depolarization preceded changes in cell membrane conductance by 3–4 s. We conclude that uncouplers excite the carotid body by inhibiting a background K+ conductance and inducing a small inward current, both of which lead to membrane depolarization and voltage‐gated Ca2+ entry. These effects are unlikely to be caused by cell acidification. The inhibition of background K+ current may be related to the uncoupling of oxidative phosphorylation.

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Section: Discussion Effects Of Uncouplers On [Ca¥]é Regulationsupporting

confidence: 73%

Section: Cause Of Uncoupler-induced Rise In [Ca¥]ésupporting

confidence: 80%

Section: Effect Of Uncouplers Upon Phécontrasting

confidence: 55%

Section: Cause Of Uncoupler-induced Rise In [Ca¥]émentioning

confidence: 99%

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Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells

Buckler

Vaughan‐Jones

1998

The Journal of Physiology

171

120

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“…Such findings have led to the suggestion that acidosis, like hypoxia, evokes secretion from type I cells via membrane depolarization and subsequent Ca¥ influx through voltage-gated Ca¥ channels. However, such a mechanism has not yet been directly demonstrated, and there is evidence in the rabbit type I cell that acidevoked transmitter release arises from accumulation of intracellular Na¤ (due to stimulation of Na¤-H¤ exchange) which is sufficient to reverse Na¤-Ca¥ exchange (Rocher et al 1991), thereby allowing Ca¥ entry via transporters rather than ion channels. Thus, it was of importance to investigate the mechanism underlying acid-evoked secretion in PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

Acid‐evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia‐evoked secretion

Taylor

Roberts

Peers

1999

The Journal of Physiology

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The carotid body is the major arterial chemoreceptor and responds to physiological stimuli (hypoxia, hypercapnia, acidosis) by increasing the discharge frequency of afferent chemosensory neurons, thereby initiating corrective changes in breathing pattern (Fidone & Gonzalez, 1986;Gonzalez et al. 1994). Type I (glomus) cells within the carotid body are central to this chemoreceptive process, releasing transmitters -particularly catecholamines -in response to physiological stimuli in a manner which correlates well with increased chemosensory nerve activity (reviewed by Gonzalez et al. 1994). Patch-clamp recordings have shown that type I cells possess Oµ-sensitive K¤ channels whose activity is reduced under hypoxic conditions (Lopez-Barneo et al. 1988;Delpiano & Hescheler, 1989;Peers, 1990a;Stea & Nurse, 1991). Such an effect causes membrane depolarization, opening of voltage-gated Ca¥ channels (Buckler & Vaughan-Jones, 1994a;Wyatt & Peers, 1995) and thus transmitter release (Urena et al. 1994). In the rat model, evidence suggests that acidicÏhypercapnic stimuli evoke transmitter release via a similar mechanism (Peers, 1990b;Peers & Green, 1991; Buckler & Vaughan-Jones, 1994b) although in the rabbit model, a completely different mechanism has been put forward to account for transduction of acidic stimuli (Rocher et al. 1991). Hypoxic and acidic stimuli are well-known to be multiplicative in their ability to increase afferent chemosensory nerve discharge (Fitzgerald & Parks, 1971;Lahiri & Delaney, 1975), an effect which may account for the well-known postnatal maturation of this sensory organ (Pepper et al. 1995). However, no explanation has been forwarded to account for this interactive effect at the cellular level, and it remains unknown whether this interaction occurs within the type I cell or involves other cellular elements of the carotid body. Recently, evidence has emerged that the rat phaeochromocytoma (PC12) cell line responds to hypoxia in a manner which is remarkably similar to that of the type I carotid body cell. Thus, hypoxia inhibits K¤ channels in these cells, causing membrane depolarization and a subsequent rise in [Ca¥]é (Zhu et al. 1996;Conforti & Millhorn, 1997). In addition, we have shown that hypoxia evokes quantal secretion of catecholamines from PC12 cells, which is entirely dependent on Ca¥ influx through voltage-

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Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

Kumar

Prabhakar

2012

Comprehensive Physiology

465

572

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The discovery of the sensory nature of the carotid body dates back to the beginning of the 20th century. Following these seminal discoveries, research into carotid body mechanisms moved forward progressively through the 20th century, with many descriptions of the ultrastructure of the organ and stimulus-response measurements at the level of the whole organ. The later part of 20th century witnessed the first descriptions of the cellular responses and electrophysiology of isolated and cultured type I and type II cells, and there now exist a number of testable hypotheses of chemotransduction. The goal of this article is to provide a comprehensive review of current concepts on sensory transduction and transmission of the hypoxic stimulus at the carotid body with an emphasis on integrating cellular mechanisms with the whole organ responses and highlighting the gaps or discrepancies in our knowledge. It is increasingly evident that in addition to hypoxia, the carotid body responds to a wide variety of blood-borne stimuli, including reduced glucose and immune-related cytokines and we therefore also consider the evidence for a polymodal function of the carotid body and its implications. It is clear that the sensory function of the carotid body exhibits considerable plasticity in response to the chronic perturbations in environmental O2 that is associated with many physiological and pathological conditions. The mechanisms and consequences of carotid body plasticity in health and disease are discussed in the final sections of this article.

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Ionic mechanisms for the transduction of acidic stimuli in rabbit carotid body glomus cells.

Cited by 68 publications

References 36 publications

Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells

Effects of mitochondrial uncouplers on intracellular calcium, pH and membrane potential in rat carotid body type I cells

Acid‐evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia‐evoked secretion

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

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