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Increase in cytosolic Ca2+ produced by hypoxia and other depolarizing stimuli activates a non-selective cation channel in chemoreceptor cells of rat carotid body #MMPMID24591572
Kang D; Wang J; Hogan JO; Vennekens R; Freichel M; White C; Kim D
J Physiol 2014[May]; 592 (9): 1975-92 PMID24591572show ga
The current model of O2 sensing by carotid body chemoreceptor (glomus) cells is that hypoxia inhibits the outward K(+) current and causes cell depolarization, Ca(2+) influx via voltage-dependent Ca(2+) channels and a rise in intracellular [Ca(2+)] ([Ca(2+)]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 approximately 20 pS channel in isolated glomus cells. The 20 pS channel was permeable to K(+), Na(+) and Cs(+) but not to Cl(-) or Ca(2+). 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 Ca(2+) channel with FPL64176 activated the 20 pS channel when 1 mm Ca(2+) was present in the external solution. Ca(2+) (10 mum) applied to the cytosolic side of inside-out patches activated the 20 pS channel. The threshold [Ca(2+)]i for activation of the 20 pS channel in cell-attached patches was approximately 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 [Ca(2+)]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.
|Animals[MESH]
|Calcium/*metabolism[MESH]
|Carotid Body/*metabolism[MESH]
|Cell Hypoxia/physiology[MESH]
|Chemoreceptor Cells/*metabolism[MESH]
|Cytosol/*metabolism[MESH]
|Female[MESH]
|Male[MESH]
|Mice[MESH]
|Mice, Inbred C57BL[MESH]
|Mice, Knockout[MESH]
|Nerve Tissue Proteins/*metabolism[MESH]
|Potassium Channels, Tandem Pore Domain/*metabolism[MESH]
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J+Physiol 2014 ; 592 (9): 1975-92
