Ca2+oscillations in rat carotid body type 1 cells in normoxia and hypoxia

Abstract

We studied the mechanisms by which carotid body glomus (type 1) cells produce spontaneous Ca2+oscillations in normoxia and hypoxia. In cells perfused with normoxic solution at 37°C, we observed relatively uniform, low-frequency Ca2+oscillations in >60% of cells, with each cell showing its own intrinsic frequency and amplitude. The mean frequency and amplitude of Ca2+oscillations were 0.6 ± 0.1 Hz and 180 ± 42 nM, respectively. The duration of each Ca2+oscillation ranged from 14 to 26 s (mean of ∼20 s). Inhibition of inositol (1,4,5)-trisphosphate receptor and store-operated Ca2+entry (SOCE) using 2-APB abolished Ca2+oscillations. Inhibition of endoplasmic reticulum Ca2+-ATPase (SERCA) using thapsigargin abolished Ca2+oscillations. ML-9, an inhibitor of STIM1 translocation, also strongly reduced Ca2+oscillations. Inhibitors of L- and T-type Ca2+channels (Cav; verapamil>nifedipine>TTA-P2) markedly reduced the frequency of Ca2+oscillations. Thus, Ca2+oscillations observed in normoxia were caused by cyclical Ca2+fluxes at the ER, which was supported by Ca2+influx via Ca2+channels. Hypoxia (2–5% O2) increased the frequency and amplitude of Ca2+oscillations, and Cavinhibitors (verapamil>nifedipine>>TTA-P2) reduced these effects of hypoxia. Our study shows that Ca2+oscillations represent the basic Ca2+signaling mechanism in normoxia and hypoxia in CB glomus cells.