Zinc modulates transient outward current gating in hippocampal neurons.
The actions of zinc ions (Zn2+) on transient outward current (TOC) were studied in cultured embryonic rat hippocampal neurons and adult guinea pig CA1 neurons acutely isolated from hippocampal slices. Zn2+ (1-1000 microM) shifted both the activation and inactivation curves for the TOC in the depolarizing direction. These effects of Zn2+ were modeled, assuming a single class of binding sites for Zn2+, yielding apparent dissociation constants for Zn2+ between 10 and 35 microM. In addition, the activation kinetics of the TOC were significantly slowed by Zn2+; deactivation was slowed at the highest concentrations of Zn2. These complex actions of Zn2+ on the TOC are likely to delay repolarization and promote spontaneous activity, resulting in action potential prolongation and hyperexcitability of hippocampal neurons.
Harrison
N L
NL
Department of Anesthesia and Critical Care, University of Chicago, IL 60637.
Radke
H K
HK
Talukder
G
G
Ffrench-Mullen
J M
JM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D015221:Potassium Channels; D015032:Zinc