ATP-sensitive K+ channels mediate an IPSP in dorsal horn neurones elicited by sensory stimulation.
Nociceptive dorsal horn neurones, which are involved in the processing of pain-related information, are inhibited by input from vibration-sensitive, large diameter primary sensory fibres (Wall and Cronly-Dillon, 1960; Salter and Henry, 1990a,b). We have reported previously that the inhibition of spinal nociceptive neurones by vibration is mediated by adenosine acting through P1-purinergic receptors (Salter and Henry, 1987). In a number of different types of cell, adenosine is known to activate K+ currents (Gerber et al., 1989; Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987) and we have recently found that the adenosine-mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP), which is, indeed, caused by a K+ conductance (De Koninck and Henry, 1988, 1992). It has been reported that adenosine-activated K+ channels in cardiac muscle cells are the ATP-sensitive K+ channels (Kirsch et al., 1990). Therefore, we questioned whether these channels might mediate the purinergic IPSP we have observed in nociceptive dorsal horn neurones. We report here that glibenclamide, a blocker of ATP-sensitive K+ channels (Ashcroft, 1988; Schmid Antomarchi et al., 1987a,b), blocks the inhibition of nociceptive neurones by vibratory stimulation when this compound is administered locally by iontophoresis or systemically by intravenous injection. In addition, direct intracellular injection of ATP was found to block the IPSP evoked by vibratory stimulation. These data indicate that the purinergic IPSP in nociceptive spinal neurones is mediated via ATP-sensitive K+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Salter
M W
MW
Division of Neuroscience, Hospital for Sick Children, Toronto, Ontario, Canada.
De Koninck
Y
Y
Henry
J L
JL
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002415:Cats; D005905:Glyburide / Q000494:pharmacology; D007478:Iontophoresis; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D010812:Physical Stimulation; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D014732:Vibration
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D005905:Glyburide