The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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)
  • Received : 2016.05.31
  • Accepted : 2016.07.07
  • Published : 2016.09.01
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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.

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References

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