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

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