Hypoxic suppression of K+ currents in type I carotid body cells: Selective effect on the Ca2+-activated K+ current

Peers, Chris

doi:10.1016/0304-3940(90)90846-2

Cited by 269 publications

(215 citation statements)

References 14 publications

Supporting

Mentioning

197

Contrasting

Unclassified

Order By: Relevance

“…This finding suggests that, unless whole-cell recording induced the patch-clamped cell to uncouple, the degree of electrical coupling between neighboring glomus cells is not high. As shown before in dispersed cells (4,27), the macroscopic K ϩ current was reversibly reduced by exposure to relatively low concentrations of TEA (Fig. 2 A Bottom).…”

Section: Figuresupporting

confidence: 81%

“…This similarity contrasts with the lack of TEA effect on dispersed rat glomus cells (18) and indicates that direct blockade of O 2 -sensitive voltage-dependent K ϩ channels, which in these cells are those blocked by TEA or IbTX (4,17,27,28), can lead to secretion. A corollary of these data is that inhibition of voltage-dependent K ϩ channels by hypoxia can contribute to initiation of the secretory response elicited by low P O 2 .…”

Section: Discussionmentioning

confidence: 78%

“…In neonatal and adult cells, the major contributors to the O 2 -sensitive macroscopic K ϩ current are voltage-and Ca 2ϩ -dependent K ϩ channels, which are blocked by external TEA (4,17,20,27). For this reason, we tested to see whether application of TEA elicited a secretory response similar to that triggered by hypoxia.…”

Section: Figurementioning

confidence: 99%

“…carotid-body slice ͉ O2 sensing ͉ glomus cell secretion A decade has passed since patch-clamp experiments on dispersed glomus cells from rabbit and rat carotid bodies showed that they were electrically excitable and contained O 2 -sensitive voltage-dependent K ϩ channels (1)(2)(3)(4)(5)(6). Although some of the electrophysiological properties and the kind of O 2 -sensitive K ϩ channel of glomus cells varied among animal species, these observations gave strong support to a unified membrane model of chemotransduction based on the capability of glomus cells to sense reductions of O 2 tension (P O 2 ) through the closure of K ϩ channels, which in turn lead to Ca 2ϩ influx, transmitter release, and activation of the afferent fibers of the sinus nerve (see refs.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium

Pardal

Ludewig

Garcı́a-Hirschfeld

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

121

123

View full text Add to dashboard Cite

We have developed a thin-slice preparation of whole rat carotid body that allows us to perform patch-clamp recording of membrane ionic currents and to monitor catecholamine secretion by amperometry in single glomus cells under direct visual control. In normoxic conditions (PO 2 Ϸ 140 mmHg; 1 mmHg ‫؍‬ 133 Pa), most glomus cells did not have measurable secretory activity, but exposure to hypoxia (P O 2 Ϸ 20 mmHg) elicited the appearance of a large number of spike-like exocytotic events. This neurosecretory response to hypoxia was fully reversible and required extracellular Ca 2؉ influx. The average charge of single quantal events was 46 ؎ 25 fC (n ‫؍‬ 218), which yields an estimate of Ϸ140,000 catecholamine molecules per vesicle. Addition of tetraethylammonium (TEA; 2-5 mM) to the extracellular solution induced in most (>95%) cells tested (n ‫؍‬ 32) a secretory response similar to that elicited by low PO 2 . Cells nonresponsive to hypoxia but activated by exposure to high external K ؉ were also stimulated by TEA. A secretory response similar to the responses to hypoxia and TEA was also observed after treatment of the cells with iberiotoxin to block selectively Ca 2؉ -and voltage-activated maxi-K ؉ channels. Our data further show that membrane ion channels are critically involved in sensory transduction in the carotid body. We also show that in intact glomus cells inhibition of voltage-dependent K ؉ channels can contribute to initiation of the secretory response to low P O 2 .carotid-body slice ͉ O2 sensing ͉ glomus cell secretion

show abstract

Section: Figuresupporting

confidence: 81%

Section: Discussionmentioning

confidence: 78%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium

Pardal

Ludewig

Garcı́a-Hirschfeld

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

121

123

View full text Add to dashboard Cite

show abstract

“…At least, there appear to be two distinct K + channels that respond to hypoxia thus causing depolarisation; firstly a high-conductance, Ca 2+ -activated K + (maxiK or BK) channel (Peers, C. 1990;Pardal, R. et al 2000;Riesco-Fagundo, A. M. et al 2001) and secondly, an acid-sensitive tandem P domain K + channel, TASK (Buckler, K. J. et al 2000). The properties of these two channels and their functional role in hypoxic signalling are described in detail in the chapters by Peers and Buckler in this issue.…”

Section: Kv Channels In Rat Cbmentioning

confidence: 99%

Oxygen sensitive Kv channels in the carotid body

López‐López

Pérez-Garcı́a

2007

Respiratory Physiology & Neurobiology

View full text Add to dashboard Cite

Hypoxic inhibition of K+ channels has been documented in many native chemoreceptor cells, and is crucial to initiate reflexes directed to improve tissue O2 supply. In the carotid body (CB) chemoreceptors, it is a general consensus regarding the facts that a decrease in pO2 leads to membrane depolarization, increase of Ca2+ entry trough voltage-dependent Ca2+ channels and Ca2+-dependent release of neurotransmitters. Central to this pathway is the modulation by hypoxia of K+ channels that triggers depolarization. However, the details of this process are still controversial, and even the molecular nature of these oxygen-sensitive K+ (KO2) channels in the CB is hotly debated. Clearly there are inter-species differences, and even in the same preparation more that one KO2 may be present. Here we recapitulate our present knowledge of the role of voltage dependent K+ channels as KO2 in the CB from different species, and their functional contribution to cell excitability in response to acute and chronic exposure to hypoxia. Dear Dr Scheid:We have been very pleased to accept Drs. Kumar and Prabhakar invitation to contribute to a Special Issue on the physiology an pathophysiology of the carotid body. Following their instructions, we have written a review paper focused on the role of voltagedependent potassium channels as oxygen-modulated ion channels in the carotid body. We have tried to make an up to date account of all the data available in the literature to provide an overview of our knowledge regarding the presence, the molecular and functional characterization and the role in oxygen chemotransduction in the carotid body of these channels.This review is an original work that has not been published elsewhere, co-authored by Dr. J.R. López-López and myself. AbstractHypoxic inhibition of K + channels has been documented in many native chemoreceptor cells, and is crucial to initiate reflexes directed to improve tissue O 2 supply. In the carotid body (CB) chemoreceptors, it is a general consensus regarding the facts that a decrease in pO 2 leads to membrane depolarization, increase of Ca 2+ entry trough voltage-dependent Ca 2+ channels and Ca 2+ -dependent release of neurotransmitters. Central to this pathway is the modulation by hypoxia of K + channels that triggers depolarization. However, the details of this process are still controversial, and even the molecular nature of these oxygen-sensitive K + (K O2 ) channels in the CB is hotly debated. Clearly there are inter-species differences, and even in the same preparation more that one K O2 may be present. Here we recapitulate our present knowledge of the role of voltage dependent K + channels as K O2 in the CB from different species, and their functional contribution to cell excitability in response to acute and chronic exposure to hypoxia.

show abstract

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

Kumar

Prabhakar

2012

Comprehensive Physiology

455

572

View full text Add to dashboard Cite

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.

show abstract

Hypoxic suppression of K+ currents in type I carotid body cells: Selective effect on the Ca2+-activated K+ current

Cited by 269 publications

References 14 publications

Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium

Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium

Oxygen sensitive Kv channels in the carotid body

Peripheral Chemoreceptors: Function and Plasticity of the Carotid Body

Contact Info

Product

Resources

About