Figure 4. Effects of chronic opioid exposure on CO₂ sensitivity in neonatal rat AMCs.

In control neonatal AMCs cultured for ∼1 week, isohydric hypercapnia (10% CO₂; pH 7.4) typically causes inhibition of outward K⁺ current (top trace) and membrane depolarization (bottom trace); current density (pA/pF) versus voltage (I–V) plot (middle) shows significant inhibition of outward current (P < 0.05) at positive potentials (A). These responses are markedly reduced or abolished in neonatal AMCs chronically exposed for ∼1 week to either a combination of μ-, δ- and κ-opioid agonists (2 μm) (B), or to either μ- or δ-opioid agonists (2 μm) alone (D and E, respectively). These blunting effects of chronic opioids on the CO₂-induced responses are prevented during continuous co-incubation with the general opioid receptor antagonist naloxone (2 μm) (C). Also, chronic exposure to the κ-opioid agonist (2 μm) alone was ineffective (F). Data are presented as mean ± SEM (n= 11). TTX was present in the extracellular solution. C, control; W, wash.