DAMGO modulates two-pore domain K<sup>+</sup> channels in the substantia gelatinosa neurons of rat spinal cord
DAMGO modulates two-pore domain K<sup>+</sup> channels in the substantia gelatinosa neurons of rat spinal cord
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제20권 제5호
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2016.01525 - 531 (7 pages)
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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<sup>+ </sup>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<sup>+</sup> 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 ofthe 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<sup>+</sup> equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying K<sup>+ </sup>channel) related acid-sensitive K<sup>+</sup> channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced K<sup>+</sup> 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<sup>+</sup> channel (TASK1 and 3) in addition to inwardly rectifying K<sup>+ </sup>channel.
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