Received for publication June 28, 2004.
Revised July 27, 2004.
Accepted for publication July 27, 2004.

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

Abstract

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 DAMGO (1-10 µM) and morphine (1-10 µM) had a greater effect on high voltage-activated Ca²⁺ currents in IB₄-negative than IB4-positive cells. However, DAMGO had no significant effect on low voltage-gated (T-type) Ca²⁺ currents in both IB₄-positive and -negative neurons. The -conotoxin GVIA-sensitive 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 significant effect on nimodipine-sensitive L-type and drug-resistant R-type Ca²⁺ currents in both groups, it produced a significantly larger inhibition on -conotoxin GVIA-sensitive N-type and -conotoxin MVIIC/-agatoxin IVA-sensitive P/Q-type Ca²⁺ currents in IB₄-negative than IB₄-positive neurons. Furthermore, double labeling of IB₄ and opioid receptors 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.

Key words: analgesia, neurotrophins, nociceptors, opioids, pain, sensory neurons

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