Open AccessOpposing mechanisms of regulation of a G-protein-coupled inward rectifier K+ channel in rat brain neurons.
Author(s) -
Bratislav M. Velimirovic,
Konomi Koyano,
Shigehiro Nakajima,
Yoshiaki Nakajima
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.5.1590
Subject(s) - g protein , pertussis toxin , locus coeruleus , inward rectifier potassium ion channel , conductance , biophysics , gtp' , chemistry , guanosine , electrophysiology , gtp binding protein regulators , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry , signal transduction , neuroscience , receptor , central nervous system , ion channel , physics , condensed matter physics , enzyme
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.