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

Abstract

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. © 2009 International Society for Neurochemistry.