title: Muscarinic receptor activation of potassium channels in rat dentate gyrus neurons.
abstract: 1. The effects of acetylcholine (ACh) on granule cells freshly dissociated from rat dentate gyrus (DG) were studied using the nystatin perforated patch technique. This method allowed us to study ACh-induced currents (IACh) under voltage clamp without "run-down" of the ACh response. In some experiments, we used the conventional whole-cell method for intracellular application of drugs not permeable to cell membrane. 2. At a holding potential of -40 mV, ACh induced an outward current. The amplitude of IACh increased in a sigmoidal fashion with increasing ACh concentration. The half-maximal response and the Hill coefficient determined from the relation between ACh concentration and response were 4.98 x 10(-7) M and 1.70, respectively. 3. The reversal potential of IACh was close to the K+ equilibrium potential. The IACh was accompanied by an enhancement of the K+ current. 4. Muscarine and McN-A-343 mimicked the ACh response, whereas oxotremorine induced no response. 5. Muscarinic antagonists reversibly suppressed the IACh (10(-5) M) in a concentration-dependent manner, where the values of half-inhibition concentration (IC50) were 1.03 x 10(-6) M for pirenzepine and 2.21 x 10(-5) M for AF-DX-116. 6. Intracellular perfusion with GDP-beta S suppressed the IACh greatly. The IACh persisted in the neurons pretreated with an external solution containing pertussis toxin (IAP) for 18 h. 7. In the neurons perfused with Ca(2+)-free external solution containing 2 mM ethylene glycol-O,O'-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM Mg2+, the first application of ACh induced the IACh with an amplitude similar to that in the standard solution.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nabekura
authors.forename: S
authors.initials: S
authors.lastname: Ebihara
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007293:Inosine Triphosphate / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D018727:Muscarinic Antagonists; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010277:Parasympathomimetics; D015221:Potassium Channels; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D007293:Inosine Triphosphate; D037342:Pertussis Toxin; D000109:Acetylcholine