Differential sensitivity of N- and P/Q-type Ca²⁺ channel currents to a μ opioid in isolectin B₄-positive and -negative dorsal root ganglion neurons

Opioids have a selective effect on nociception with little effect on other sensory modalities. However, the cellular mechanisms for this preferential effect are not fully known. Two broad classes of nociceptors can be distinguished based on their growth factor requirements and binding to isolectin B₄ (IB₄). In this study, we determined the difference in the modulation of voltage-gated Ca²⁺ currents by [D-Ala ²,N-Me-Phe⁴,Gly-ol⁵]-enkephalin (DAMGO, a specific μ oploid agonist) between IB₄-positive and -negative small dorsal root ganglion (DRG) neurons. Whole-cell voltage-clamp recordings were performed in acutely isolated DRG neurons in adult rats. Both 1-10 μM DAMGO and 1 to 10 μM morphine had a greater effect on high voltage-activated Ca²⁺ currents in IB₄-negative than IB4-positive cells. However, DAMGO had no significant effect on T-type Ca²⁺ currents in both groups. The N-type Ca²⁺ current was the major subtype of Ca ²⁺ currents inhibited by DAMGO in both IB₄-positive and -negative neurons. Although DAMGO had no effect on L-type and R-type Ca ²⁺ currents in both groups, it produced a larger inhibition on N-type and P/Q-type Ca²⁺ currents in IB₄-negative than IB ₄-positive neurons. Furthermore, double labeling revealed that there was a significantly higher μ opioid receptor immunoreactivity in IB ₄-negative than IB₄-positive cells. Thus, these data suggest that N-and P/Q-type Ca²⁺ currents are more sensitive to inhibition by the μ opioids in IB₄-negative than IB ₄-positive DRG neurons. The differential sensitivity of voltage-gated Ca²⁺ channels to the μ opioids in subsets of DRG neurons may constitute an important analgesic mechanism of μ opioids.