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http://dx.doi.org/10.4196/kjpp.2016.20.5.525

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

Cho, Pyung Sun (Department of Biomedical Science, Graduate School of Biomedical Science, Engineering, Hanyang University)
Lee, Han Kyu (Department of Biomedical Science, Graduate School of Biomedical Science, Engineering, Hanyang University)
Lee, Sang Hoon (Department of Biomedical Science, Graduate School of Biomedical Science, Engineering, Hanyang University)
Im, Jay Zoon (Department of Biomedical Science, Graduate School of Biomedical Science, Engineering, Hanyang University)
Jung, Sung Jun (Department of Biomedical Science, Graduate School of Biomedical Science, Engineering, Hanyang University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.20, no.5, 2016 , pp. 525-531 More about this Journal
Abstract
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 ${\mu}$-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.
Keywords
DAMGO; $K^+$ current; Opioid; SG neuron; TASK;
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