Differential Sensitivity of Carotid Body Glomus Cells to Hypoxia and Acidosis

Abstract

We recently demonstrated that TASK channels known to transduce the effect of hypoxia on carotid body glomus cells also contribute to sensing low pH (Circ Res 101, 1009‐1019, 2007). In this study we contrasted the effects of hypoxia (pO2=15 mmHg) and acidosis (pH 6.8) on cytosolic Ca2+ concentration in clusters of glomus cells dissociated from carotid bodies of rats. The cells were loaded with Fluo‐4/AM, a single wavelength fluorescent Ca2+ probe. A microscope (Nikon TE2000‐U) equipped with a CCD camera (Photometrics Cool SNAP‐cf) and imaging analysis software (MetaMorph 6.1) were used to quantitate [Ca2+]i. Baseline [Ca2+]i ranged from 40 to 76 nM (mean 53 ± 2 nM) in 33 glomus cells tested from 7 clusters. Transient increases in [Ca2+]i (?) ranging from 20 to 245 nM were seen in 19 responsive cells. Of these cells, 13 responded to hypoxia (? = 82 ± 17 nM) and 11 cells responded to low pH (? = 111 ± 26 nM). Eight of the 13 hypoxia‐sensitive cells had an increase in [Ca2+]i of 75 ± 24 nM but did not respond to pH 6.8. Conversely, 5 of the 11 pH‐sensitive cells were highly responsive to low pH (? =163 ± 31 nM, n = 5) but showed negligible responses to hypoxia. The results indicate a significant degree of selectivity in responsiveness of individual glomus cells to hypoxia vs. low pH and suggest alternative transduction pathways for hypoxia and acidosis in carotid body chemoreceptors. (HL14388).