Opposing mechanisms of regulation of a G-protein-coupled inward rectifier K+ channel in rat brain neurons.
In locus coeruleus neurons, substance P (SP) suppresses an inwardly rectifying K+ current via a pertussis toxin-insensitive guanine nucleotide binding protein (G protein; GnonPTX), whereas somatostatin (SOM) or [Met]enkephalin (MENK) enhances it via a pertussis toxin-sensitive G protein (GPTX). The interaction of the SP and the SOM (or MENK) effects was studied in cultured locus coeruleus neurons. In neurons loaded with guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), application of SOM (or MENK) evoked a persistent increase in the inward rectifier K+ conductance. A subsequent application of SP suppressed this conductance to a level less than that before the SOM (or MENK) application; the final conductance level was independent of the magnitude of the SOM (or MENK) response. This suppression by SP was persistent, and a subsequent SOM (or MENK) application did not reverse it. When SP was applied to GTP[gamma S]-loaded cells first, subsequent SOM elicited only a small response. In GTP-loaded neurons, application of SP temporarily suppressed the subsequent SOM- (or MENK)-induced conductance increase. These results suggest that the same inward rectifier molecule that responds to an opening signal from GPTX also responds to a closing signal from GnonPTX. The closing signal is stronger than the opening signal.
Velimirovic
B M
BM
Department of Pharmacology, University of Illinois, College of Medicine at Chicago 60612.
Koyano
K
K
Nakajima
S
S
Nakajima
Y
Y
D000818:Animals; D016275:Atrial Function; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D008125:Locus Coeruleus / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*
D015221:Potassium Channels; D013373:Substance P; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; D004744:Enkephalin, Methionine; D019204:GTP-Binding Proteins