The effect of hypercapnia on outwardly-rectifying currents was examined in locus coeruleus (LC) neurons in slices from neonatal rats (P3-P15). Two outwardly-rectifying currents (4-aminopyridine [4-AP]-sensitive transient current and tetraethyl ammonium [TEA]-sensitive sustained current) were found in LC neurons. 4-AP induced a membrane depolarization of 3.6 ± 0.6mV (n = 4), while TEA induced a smaller membrane depolarization of 1.2 ± 0.3 mV (n = 4). Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the TEA-sensitive current was reduced by 52.1 ± 4.5% (n=5) in 15% CO₂ (pH_o 7.00, pH_i 6.96). The maximal amplitude of the 4-AP-sensitive current was reduced by 34.5 ± 3.0% (n = 6) in 15% CO₂ (pH_o 7.00, pH_i 6.96), by 29.4 ± 6.8% (n = 6) in 10% CO₂ (pH_o 7.15, pH_i 7.14), and increased by 29.0 ± 6.4% (n = 6) in 2.5% CO₂ (pH_o 7.75, pH_i 7.35). 4-AP completely blocked hypercapnia-induced increased firing rate but TEA did not affect it. When LC neurons were exposed to HA with either pHo or pHi constant, the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive current (likely an A current) is inhibited by decreases in either pH_o or pH_i. The inhibition of the A current by various levels of CO₂ is correlated with the change in firing rate induced by CO₂, implicating the 4-AP-sensitive current in chemosensitive signaling in LC neurons.