Ca 2+ 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.