Serotonin-operated potassium current in CA1 neurons dissociated from rat hippocampus.
1. The intracellular mechanisms of serotonin (5-HT) response were investigated in dissociated rat hippocampal pyramidal neurons using the nystatin-perforated patch technique. 2. Under voltage-clamp conditions, 5-HT evoked outward currents (I5-HT) with an increase in membrane conductance at a holding potential of -40 mV. The outward current reversed at the K+ equilibrium potential, which shifted 59.4 mV with a 10-fold change in extracellular K+ concentration. 3. The first application of 5-HT on neurons perfused with Ca(2+)-free external solution induced outward currents of I5-HT but the amplitude was diminished dramatically with successive applications. Pretreatment with the membrane-permeant Ca2+ chelator 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester (BAPTA-AM) also diminished the I5-HT amplitude. 4. Pretreatment with pertussis toxin (PTX) had no effect on I5-HT. 5. The I5-HT was not cross-desensitized with the caffeine-induced outward current but with outward current mediated by the muscarinic acetylcholine receptor. Pretreatment with Li+ significantly enhanced the I5-HT, indicating that I5-HT is involved in the elevation of intracellular free Ca2+ released from inositol triphosphate (IP3)-sensitive Ca2+ store sites but not from the caffeine-sensitive ones. 6. The calmodulin (CaM) antagonists, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), inhibited I5-HT in a concentration-dependent manner. 7. The Ca2+/CaM-dependent protein kinase II inhibitor 1-[N,O-Bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosil]-4-phenylpiperazine depressed the I5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
H
H
Uneyama
S
S
Ueno
N
N
Akaike
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
D002147:Calmodulin; D015221:Potassium Channels; D011985:Receptors, Serotonin; D012701:Serotonin; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D011188:Potassium; D002118:Calcium