Abstract
ATP-sensitive K+ (KATP) channels were reported to be involved in morphine analgesia in vivo. The present study, using patch-clamp technique in brain slices of neonatal (P12-P16) and adult rats, investigated cellular actions of KATP channel ligands and their interactions with morphine in the ventrolateral periaqueductal gray (PAG), a crucial site for morphine analgesia. In neonatal PAG neurons, morphine depressed evoked inhibitory postsynaptic currents (IPSCs) in almost all tested neurons and elicited an inwardly rectifying K+ current in one-third of tested neurons. Glibenclamide (1–10 μM), a KATP channel blocker, did not affect the membrane current or synaptic current per se but also failed to affect the effects of morphine. No outward current was elicited upon using microelectrodes containing ATP-free internal solution. In adult neurons, morphine, at the concentration up to 300 μM, failed to activate K+ current in all 25 neurons tested but depressed IPSCs to a comparable extent as that in neonatal neurons. Glibenclamide also failed to alter the effect of morphine in adult neurons. The openers of KATP channels, lemakalim (10–30 μM) and diazoxide (10–500 μM), unlike morphine, did not increase membrane currents in both neonatal and adult neurons. However, diazoxide induced a glibenclamide-sensitive outward current in hippocampal CA1 neurons. It is concluded that KATP channels display little functional role per se and might not be involved in effects of morphine in the ventrolateral PAG. The correlation between the insensitivity in K+ channel activation and the less antinociceptive response to morphine in adults was discussed.
Footnotes
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This work was supported by Grant NSC 89-2320-B-002-273 from National Science Council, Republic of China, and Grant NHRI-EX90-905NC from National Health Research Institutes (to L.C.C.).
- Abbreviations:
- KATP
- ATP-sensitive K+
- PAG
- periaqueductal gray
- ACSF
- artificial cerebral spinal fluid
- EPSC
- excitatory postsynaptic current
- IPSC
- inhibitory postsynaptic current
- Ihold
- holding current
- Received January 8, 2001.
- Accepted April 10, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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