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NEUROPHARMACOLOGY

Differential Sensitivity of N- and P/Q-Type Ca²+ Channel Currents to a µ Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons

Department of Anesthesiology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania

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-Ala²,N-Me-Phe⁴,Gly-ol⁵]-enkephalin (DAMGO, a specific µ opioid 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 Ca²⁺ currents inhibited by DAMGO in both IB₄-positive and -negative neurons. Although DAMGO had no effect on L-type and R-type Ca²⁺ currents in both groups, it produced a larger inhibition on N-type and P/Q-type Ca²⁺ currents in IB₄-negative than IB₄-positive neurons. Furthermore, double labeling revealed that there was a significantly higher µ opioid receptor immunoreactivity in IB₄-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 IB₄-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.

Address correspondence to: Dr. Hui-Lin Pan, Department of Anesthesiology, H187, The Pennsylvania State University College of Medicine, 500 University Dr., Hershey, PA 17033-0850. E-mail: hpan{at}psu.edu

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