Bicuculline-resistant, Cl- dependent GABA response in the rat spinal dorsal horn.
Receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the mammalian central nervous system (CNS), have been divided into three subtypes. GABA(A) receptor is a ligand-gated chloride channel that is competitively antagonized by bicuculline, whereas GABA(B) receptor regulate Ca2+ or K+ channels through G proteins. Recently, GABA(C) receptor has been identified in mammalian and fish retina. Unlike GABA(A) receptors, the GABA(C) receptor is a bicuculline-resistant chloride channel that is selectively activated by cis-4-aminocrotonic acid (CACA), and antagonized by imidazole-4-acetic acid (I4AA) and to some extent by picrotoxin. We report here that bicuculline-resistant GABA responses mediated by chloride channels are also expressed in substantia gelatinosa (SG) neurons in the dorsal horn, which receive predominantly nociceptive inputs from periphery. The GABA responses are, however, not mimicked by CACA nor affected by I4AA, but abolished by picrotoxin. Moreover, these responses are modulated by benzodiazepines (flunitrazepam) and barbiturates (thiopental), although GABA(C) responses are not affected. Thus, the pharmacological characteristics of the GABA responses observed in SG neurons are distinct from those responses mediated by the known GABA receptors. These differences may reflect the presence of receptor subunits unique to SG neurons.
Park
J S
JS
Department of Physiology, Saga Medical School, Japan.
Higashi
H
H
Nagata
K
K
Yoshimura
M
M
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D005445:Flunitrazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects*; D013376:Substantia Gelatinosa / Q000187:drug effects*; D013874:Thiopental / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D018118:Chloride Channels; D005445:Flunitrazepam; D018756:GABA Antagonists; D018757:GABA Modulators; D010852:Picrotoxin; D018079:Receptors, GABA; D013874:Thiopental; D005680:gamma-Aminobutyric Acid