mu-Opioid receptor activation reduces multiple components of high- threshold calcium current in rat sensory neurons

Abstract

Whole-cell patch-clamp recordings were used to characterize calcium channel types that are modulated by mu-opioid receptor activation in rat dorsal root ganglion (DRG) neurons. Five distinct components of high-threshold calcium current were isolated on the basis of their sensitivity to the selective channel blockers omega-conotoxin GVIA, nifedipine, omega-conotoxin MVIIC, or omega-agatoxin IVA. The mu-opioid selective agonist Tyr-Pro-NMePhe-D-Pro-NH2 (PLO17) routinely suppressed high-threshold currents and this effect was always reduced by omega-conotoxin GVIA. A fraction of PLO17-sensitive current remained after omega-conotoxin GVIA that was eliminated by application of omega-agatoxin IVA alone or in combination with omega-conotoxin MVIIC. Nifedipine had no effect on mu-opioid responses nor did PLO17 affect the slow component of tail current induced by Bay K 8644. These data suggest that mu-opioid receptors are negatively coupled to three types of calcium channels in rat DRG neurons, including an omega-conotoxin GVIA-sensitive (N-type) channel, an omega-agatoxin IVA-sensitive (P-type) channel and an omega-conotoxin MVIIC-sensitive, nifedipine/GVIA/omega-Aga IVA-resistant (presumptive Q-type) channel.

Differential Effects of CB1 and Opioid Agonists on Two Populations of Adult Rat Dorsal Root Ganglion Neurons

“…Other studies of calcium currents in small DRG neurons noted a greater contribution of N-type VDCCs to the total calcium current (Rusin and Moises, 1995;Wiley et al, 1997;Acosta and Lopez, 1999). The variability in results is most likely attributable to technical factors in that currents through VDCCs in previous studies were isolated by suppressing other cation currents and were evoked with brief (30 -100 msec) changes in voltage.…”

κ-Opioid Receptor Activation Modulates Ca2+Currents and Secretion in Isolated Neuroendocrine Nerve Terminals

“…Somatic recordings obtained from rat peripheral sensory (Schroeder et al, 1991;Moises et al, 1994;Rusin and Moises, 1995) and nucleus tractus solitarius neurons (Rhim and Miller, 1994) have identified several high-threshold Ca 2ϩ channels that are modulated by opioid receptors. In these neurons, -opioids, and -selective agonists to a lesser extent, inhibit Ca 2ϩ current contributed by GVIA-sensitive N-type and pharmacologically distinct P-and Q-type channels but spare L-and T-type currents, thereby regulating the principal Ca 2ϩ channel types involved in exocytosis at central synapses and peripheral sites of release (Luebke et al, 1993;Takahashi and Momiyama, 1993;Wheeler et al, 1994;Dunlap et al, 1995).…”

“…Although it remains unclear how the presynaptic inhibitory effects of opioids are manifested, measurements from neuronal somata suggest that the depression of release may result from reductions in Ca 2ϩ influx through voltage-dependent Ca 2ϩ channels (North, 1993). Activation of -, ␦-, or -opioid receptors has been shown to inhibit somatic N-and P/Q-type Ca 2ϩ currents in several types of neurons (Schroeder et al, 1991;Moises et al, 1994;Rhim and Miller, 1994;Rusin and Moises, 1995) and clonal cells (Seward et al, 1991;Taussig et al, 1992). These same channel types have been implicated to play a pivotal role in mediating Ca 2ϩ influx that triggers depolarization-evoked neurotransmitter release from nerve endings in the periphery (Kongsamut et al, 1989;Toth et al, 1993) and CNS (Takahashi and Momiyama, 1993;Turner et al, 1993;Wheeler et al, 1994).…”

Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and Are Putative Nociceptors

“…Because opioid receptors are thought to modulate several types of Ca 2ϩ channels (Rusin and Moises 1995), the expression of different types of voltage-gated Ca 2ϩ current was studied in neurons positive and negative for the Mrgprd receptor. Current-voltage plots of I Ca , run from holding potentials of Ϫ90 and Ϫ50 mV, revealed a prominent shoulder at lower membrane potentials (ՅϪ20 mV) in MrgprdϪ neurons (Fig.…”