Peripheral inflamation-induced increase of AMPA-mediated currents and Ca2+ transients in the presence of cyclothiazide in the rat substantia gelatinosa neurons.
This study employing a rodent model of acute pain investigated the influence of carrageenan-induced inflammation on the ability of S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor activation to induce membrane currents and rises in cytosolic free calcium concentration ([Ca2+]i) in the rat substantia gelatinosa (SG) neurons using simultaneous whole-cell patch-clamp recording and fura-2 calcium imaging in spinal cord slices of L4-L5 segments. The novel finding of this study is that carrageenan-induced inflammation, in the presence of cyclothiazide, an inhibitor of AMPA receptor desensitization, produces a sustained facilitation of the AMPA-mediated membrane current and rises in [Ca2+]i in both the soma and proximal dendrites of SG neurons recorded on the injected side 3 h after the induction of inflammation. These results suggest that in carrageenan-inflamed rats AMPA receptors undergo some alterations that influence AMPA receptors desensitization and/or sensitivity to cyclothiazide.
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA. nana@serv.biph.kiev.ua
N
N
Voitenko
G
G
Gerber
D
D
Youn
M
M
Randic
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001581:Benzothiadiazines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002351:Carrageenan / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013376:Substantia Gelatinosa / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002351:Carrageenan; C004639:cyclothiazide; D002118:Calcium