DAMGO modulates two-pore domain K⁺ channels in the substantia gelatinosa neurons of rat spinal cord
Pyung-Sun CHO; Han-Kyu LEE; Sang-Hoon LEE; Jay-Zoon IM; Sung-Jun JUNG; Pyung-Sun CHO; Han-Kyu LEE; Sang-Hoon LEE; Jay-Zoon IM; Sung-Jun JUNG; Pyung-Sun CHO; Han-Kyu LEE; Sang-Hoon LEE; Jay-Zoon IM; Sung-Jun JUNG.
The Korean Journal of Physiology and Pharmacology
; : 525-531, 2016.
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| WPRIM | ID: wpr-728678
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.
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