| Popis: |
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. |
