HYPOXIA INDUCES VOLTAGE-DEPENDENT CA2-BODY GLOMUS CELLS( ENTRY AND QUANTAL DOPAMINE SECRETION IN CAROTID)

We have investigated the changes of cytosolic [Ca2+] and the secretory activity in single glomus cells dispersed from rabbit carotid bodies during exposure to solutions with variable Oz tension (Pot). In normox ic conditions (Po-2 = 145 mmHg; 1 mmHg = 133 Pa), intracellular [Ca2+] was 58 +/- 29 nM, and switching to low Pot (between 10 and 60 mmHg) l ed to a reversible increase of [Ca2+] up to 800 nM. The response to hy poxia completely disappeared after removal of external Ca2+ or with th e addition of 0.2 mM Cd2+ to the external solution. These same solutio ns also abolished both the Ca2+ current of the cells and the increase of internal [Ca2+] elicited by high external K+. Elevations of cytosol ic [Ca2+] in response to hypoxia or to direct membrane depolarization elicited the release of dopamine, which was detected by amperometric t echniques. Dopamine secretion occurred in episodes of spike-like activ ity that appear to represent the release from single secretory vesicle s. From the mean charge of well-resolved secretory events, we estimate d the average number of dopamine molecules per vesicle to be approxima te to 140,000, a value about 15 times smaller than a previous estimate in chromaffin granules of adrenomedullary cells. These results direct ly demonstrate in a single-cell preparation the secretory response of glomus cells to hypoxia. The data indicate that the enhancement of cel lular excitability upon exposure to low Po-2 results in Ca2+ entry thr ough voltage-gated channels, which leads to an increase in intracellul ar [Ca2+] and exocytotic transmitter release.