J. Urena et al., HYPOXIA INDUCES VOLTAGE-DEPENDENT CA2-BODY GLOMUS CELLS( ENTRY AND QUANTAL DOPAMINE SECRETION IN CAROTID), Proceedings of the National Academy of Sciences of the United Statesof America, 91(21), 1994, pp. 10208-10211
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.