| Online-Ressource |
Verfasst von: | Kang, Dawon [VerfasserIn]  |
| Wang, Jiaju [VerfasserIn]  |
| Hogan, James O. [VerfasserIn]  |
| Vennekens, Rudi [VerfasserIn]  |
| Freichel, Marc [VerfasserIn]  |
| White, Carl [VerfasserIn]  |
| Kim, Donghee [VerfasserIn]  |
Titel: | Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body |
Verf.angabe: | Dawon Kang, Jiaju Wang, James O. Hogan, Rudi Vennekens, Marc Freichel, Carl White and Donghee Kim |
E-Jahr: | 2014 |
Jahr: | 05 March 2014 |
Umfang: | 18 S. |
Fussnoten: | Im Titel ist "2+" nach Ca hochgestellt ; Gesehen am 14.09.2020 |
Titel Quelle: | Enthalten in: The journal of physiology |
Ort Quelle: | Hoboken, NJ : Wiley-Blackwell, 1878 |
Jahr Quelle: | 2014 |
Band/Heft Quelle: | 592(2014), 9, Seite 1975-1992 |
ISSN Quelle: | 1469-7793 |
Abstract: | Key points Hypoxia is thought to depolarize glomus cells by inhibiting the outward K+ current, which sets in motion a cascade of ionic events that lead to transmitter secretion, increased afferent carotid sinus nerve activity and increased ventilation. Our study of Na+-permeable channels in glomus cells has revealed that hypoxia not only inhibits TASK background K+ channels but also indirectly activates a non-selective cation channel with a single channel conductance of 20 pS. Under physiological conditions, the reversal potential of the cation channel is ∼ -28 mV, indicating that Na+ influx is also involved in hypoxia-induced excitation of glomus cells. Activation of the 20 pS cation channel is present when the O2 content is 5% or less, indicating that Na+ influx occurs during moderate to severe hypoxia (<5% O2), but not mild hypoxia (>5% O2). The 20 pS cation channel is directly activated by a rise in intracellular Ca2+. Thus, factors that elevate intracellular Ca2+ such as hypoxia, extracellular acidosis and high external KCl all activate the cation channel. A feed-forward mechanism may be present in which an initial depolarization-induced rise in intracellular Ca2+ opens the Na+-permeable cation channel, and the Na+ influx causes additional depolarization and influx of Ca2+ into glomus cells. Abstract The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K+ current and causes cell depolarization, Ca2+ influx via voltage-dependent Ca2+ channels and a rise in intracellular [Ca2+] ([Ca2+]i). Here we show that hypoxia (<5% O2), in addition to inhibiting the two-pore domain K+ channels TASK-1/3 (TASK), indirectly activates an ∼20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K+, Na+ and Cs+ but not to Cl− or Ca2+. The 20 pS channel was not sensitive to voltage. Inhibition of TASK by external acid, depolarization of glomus cells with high external KCl (20 mm) or opening of the Ca2+ channel with FPL64176 activated the 20 pS channel when 1 mm Ca2+ was present in the external solution. Ca2+ (10 μm) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca2+]i for activation of the 20 pS channel in cell-attached patches was ∼200 nm. The reversal potential of the 20 pS channel was estimated to be −28 mV. Our results reveal a sequential mechanism in which hypoxia (<5% O2) first inhibits the K+ conductance and then activates a Na+-permeable, non-selective cation channel via depolarization-induced rise in [Ca2+]i. Our results suggest that inhibition of K+ efflux and stimulation of Na+ influx both contribute to the depolarization of glomus cells during moderate to severe hypoxia. |
DOI: | doi:10.1113/jphysiol.2013.266957 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1113/jphysiol.2013.266957 |
| Volltext: https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.2013.266957 |
| DOI: https://doi.org/10.1113/jphysiol.2013.266957 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1731799217 |
Verknüpfungen: | → Zeitschrift |
Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body / Kang, Dawon [VerfasserIn]; 05 March 2014 (Online-Ressource)