DAMGO modulates two-pore domain K(+) channels in the substantia gelatinosa neurons of rat spinal cord.
The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying K(+) current. In this study, we examined whether a µ-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain K(+) channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the K(+) equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K(+) channel) related acid-sensitive K(+) channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K(+) current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain K(+) channel (TASK1 and 3) in addition to inwardly rectifying K(+) channel.
Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul 04763, Korea.
Pyung Sun
PS
Cho
Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul 04763, Korea.
Han Kyu
HK
Lee
Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul 04763, Korea.
Sang Hoon
SH
Lee
Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul 04763, Korea.
Jay Zoon
JZ
Im
Department of Biomedical Science, Graduate School of Biomedical Science; Engineering, Hanyang University, Seoul 04763, Korea.
Sung Jun
SJ
Jung
DAMGO; K+ current; Opioid; SG neuron; TASK