Submitted on November 26, 2003
Accepted on December 27, 2004
Dopamine D2 receptor modulation of carotid body type 1 cell intracellular calcium in developing rats
John L. Carroll1*, Kathleen M. Boyle2, Michael J. Wasicko3, and Laura M. Sterni3
1 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
2 Arkansas Children's Hospital, Little Rock, Arkansas, USA
3 Johns Hopkins Children's Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
* To whom correspondence should be addressed. E-mail: carrolljohnl{at}uams.edu.
The carotid chemoreceptors contain abundant dopamine, stored in the O2-sensing type-1 cells and released in response to hypoxia and other stimuli. Most studies suggest that dopamine inhibits carotid chemoreceptor neural activity, probably via dopamine D2 autoreceptors on type 1 cells, and decreasing dopaminergic inhibition with age has been proposed as a mechanism underlying the postnatal increase in carotid chemoreceptor O2 sensitivity. The present study explores dopaminergic modulation of the intracellular calcium ([Ca2+]i) response to hypoxia in freshly dissociated clusters of carotid chemoreceptor type-1 cells from 1, 3, and 11-16 day old rats. Using the calcium-sensitive fluoroprobe fura-2, we studied the effects of quinpirole, a selective dopamine D2 receptor agonist, on the type-1 cell [Ca2+]i response to 90 second hypoxia challenges (PO2 ~1-2 mmHg). Cells were sequentially exposed to three 90 second challenges, as follows: a) hypoxia control, b) hypoxia + quinpirole, and c) hypoxia + quinpirole + sulpiride (a selective D2 receptor antagonist). In the 11-16 day old group, glomus cell [Ca2+]i increased ~3-4 fold over resting [Ca2+]i in response to hypoxia. Quinpirole (10 µM) significantly blunted the peak [Ca2+]i response to hypoxia. Repeat challenge with hypoxia + 10 µM quinpirole in the presence of 10 µM sulpiride partially restored the hypoxia [Ca2+]i response. Glomus cells from 1 and 3 day old rats had smaller [Ca2+]i elevations in response to hypoxia. In sharp contrast to the older rats, 10 µM quinpirole had only a minimal effect on the hypoxia response of glomus cells from 1 day olds and a small but significant effect at 3 days of age. We conclude that stimulation of dopamine D2 receptors inhibits the carotid glomus cell [Ca2+]i response to hypoxia, consistent with an inhibitory autoreceptor role. These findings suggest that DA-mediated inhibition and oxygen sensitivity increase with age on a similar time course and do not support a role for dopamine as a major mediator of carotid chemoreceptor resetting.
