Studies of dopamine (DA) release were conducted with 10 perfused/superfused cat carotid bodies using shallow recessed Nafion polymer-coated microsensors (tips ∼5
μm). Simultaneous measurements of tissue DA and neuronal discharge (ND) from the sinus nerve were made after switching from normoxic, normocapnic control perfusate (20% O
2, 5% CO
2, balance N
2) to a normoxic, normocapnic perfusate equilibrated with a high tension (>550 Torr) of carbon monoxide (CO). When high
P
CO perfusate was delivered in the dark, ND increased from a baseline of 89±24 (SE) impulses/s, to a peak excitation of 374±44 impulses/s within 15–30 s. Excitation then diminished to a plateau of 281±36 impulses/s within 1–2 min. Both peak and plateau ND were significantly above baseline (
P<0.05). Average tissue DA values increased above basal levels by +7.2±1.0 and +5.6±0.6
μM, respectively, during the peak and plateau ND phases (
P<0.05). Bright light restored the chemosensory activity to baseline, but had no effect on DA. Both chemosensory excitation and tissue DA responses to high CO in the dark were diminished in 3 carotid bodies perfused with Ca
2+-free solutions. Responses were reduced even further with Ca
2+ chelator (EGTA) in the perfusate. The results suggest that the effect of high
P
CO on DA release and chemosensory excitation are dependent on Ca
2+ in the media, but the two events are not coupled.