A metabolically stable analog of 1,4,5-inositol trisphosphate activates a novel K+ conductance in pyramidal cells of the rat hippocampal slice.
IP(s)3, a metabolically stable analog of 1,4,5-inositol trisphosphate (IP3), inhibited action potential firing when injected into hippocampal pyramidal cells. This effect was associated with decreased input resistance, a more negative resting potential, outward rectification at depolarized potentials, and an afterhyperpolarization. The response to IP(s)3 was unaffected by antagonists of Na+, Ca2+, and Cl- conductances, but was sensitive to changes in extracellular K+ concentration. The IP(s)3-induced conductance was voltage-dependent, was activated in 10 ms with depolarization, and was blocked by extracellular Ba2+ or intracellular Ca2+ chelation. It was not suppressed by other K+ conductance antagonists. Thus, IP(s)3 may activate a novel K+ conductance in CA1 pyramidal cells. IP3 itself did not elicit this conductance, suggesting it may be rapidly metabolized in these cells.
McCarren
M
M
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Potter
B V
BV
Miller
R J
RJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D004553:Electric Conductivity; D004594:Electrophysiology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives*; D008297:Male; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D011930:Reaction Time
D009946:Organothiophosphorus Compounds; C054737:inositol 1,4,5-triphosphorothioate; D001464:Barium; D007294:Inositol; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D002118:Calcium