DAMGO Modulates two-pore domain K+ channels in the substantia gelatinosa neurons of rat spinal cord

作者：Cho Pyung Sun; Lee Han Kyu; Lee Sang Hoon; Im Jay Zoon; Jung Sung Jun^*

来源：Korean Journal of Physiology and Pharmacology, 2016, 20(5): 525-531.

DOI：10.4196/kjpp.2016.20.5.525

• DAMGO
• K+ current
• Opioid
• SG neuron
• TASK

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 p-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 similar to V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I similar to 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.

• 出版日期2016-9