A functional link between T-type calcium channels and μ-opioid receptor expression in adult primary sensory neurons

The μ-opioid receptor agonists have a preferential effect on nociception in adults but their analgesic effect is less selective in neonates. Here we presented our finding that the μ-opioid receptor agonists had no effect on high voltage-activated Ca²⁺ channels (HVACCs) in adult dorsal root ganglion (DRG) neurons that exhibited a prominent T-type Ca²⁺ current. We also determined the mechanisms underlying the μ-opioid agonists' lack of effect on HVACCs in these neurons. The μ-opioid agonist [d-Ala ²,N-Me-Phe⁴,Gly-ol⁵]-enkephalin (DAMGO), morphine, and morphine 6-β-D-glucuronide had no effect on either T-type or HVACC currents despite the presence of a large N-type Ca²⁺ current in neurons with T-type Ca²⁺ currents. DAMGO still had no effect on HVACC currents when T-type Ca²⁺ channels were blocked in these neurons. However, intracellular dialysis of GTP-γ-S to activate G proteins significantly attenuated HVACC currents. DRG neurons with T-type Ca ²⁺ currents showed little responses to capsaicin. Single-cell RT-PCR analysis revealed that the μ-opioid receptor mRNA was present only in adult DRG neurons lacking prominent T-type Ca²⁺ currents. In the neonatal DRG, DAMGO inhibited HVACC currents in 31% neurons with T-type Ca²⁺ currents. The μ-opioid receptor mRNA was detected in all neurons without T-type Ca²⁺ currents and also in 28.6% of neurons with T-type Ca ²⁺ currents in the neonatal DRG. Our study provides novel information that adult DRG neurons with prominent T-type Ca²⁺ currents do not express μ-opioid receptors. Expression of T-type Ca²⁺ (Ca _V3.2) channels and μ-opioid receptors may be developmentally co-regulated as some DRG neurons differentiate toward becoming nociceptive neurons.