Previous studies have demonstrated that bicarbonate enhances the speed and magnitude of the carotid body chemoreceptor response to hypoxia. We hypothesized that this enhancement is associated with enhanced hypoxia-induced catecholamine (CAT) secretion from glomus cells. Single-fiber nerve activity and free tissue catecholamine (carbon fiber microvoltammetry) were measured in rat carotid body, in vitro. The peak CAT and nerve responses during 1 min anoxia were larger in the presence of bicarbonate than in its absence (peak CAT: 16.7 +/- 2.7 vs. 5.1 +/- 1.1 microM; peak nerve: 28.2 +/- 1.6 vs. 16.7 +/- 1.4 Hz). Bicarbonate particularly enhanced the responses to moderate hypoxia (PO2 approximately 80 Torr) which caused no secretion or increased nerve activity in the absence of bicarbonate, but caused significant stimulation in the presence of bicarbonate (peak nerve = 15.2 Hz; peak CAT = 8.6 microM). The bicarbonate effect was not due to alterations in intracellular pH since it was not blocked by exchanger blockers (DIDS) or mimicked by acidification of the medium. However, anion channel blockade by 9-AC or DPC reduced anoxia-induced CAT secretion in the presence of bicarbonate. We conclude that bicarbonate greatly enhances stimulus/secretion coupling in glomus cells, probably through modulation of an anion current carried by bicarbonate.