Figure 4.

A: schematic illustrating the proposed effect of opioids at excitatory synapses on rhythmogenic Dbx1 neurons. In response to MOR activation, G_βγ-mediated inhibition of voltage-gated Ca²⁺ currents reduces the probability of vesicular release in response to bouts of action potentials that occur during inspiratory bursts. B: PreBötC slices from mice with a heterozygous deletion of Ca_V 2.1 encoding P/Q-type Ca²⁺ channels are ∼10-fold more sensitive to the MOR agonist DAMGO than WT controls (data shown as median ± interquartile range). C: representative voltage clamp recordings of mEPSCs from a Dbx1 neuron following blockade of action potentials with TTX (1 µM). The frequency of mEPSCs is reduced in the presence of DAMGO (100 nM), and subsequent blockade KCNQ channels with XE991 (20 µM) restores mEPSC frequency to baseline levels. Data adapted with permission from Wei and Ramirez (20). KO, knockout; mEPSCs, miniature excitatory postsynaptic currents; MOR, mu-opioid receptor; P, probability; preBOTc, preBӧtzinger complex; WT, wild type.