Potassium-induced enhancement of persistent inward current in hippocampal neurons in isolation and in tissue slices.
Previous work suggested a role for the voltage-dependent persistent sodium current, I(Na,P), in the generation of seizures and spreading depression (SD). Ordinarily, I(Na,P) is small in hippocampal neurons. We investigated the effect of raising external K(+) concentration, [K(+)](o), on whole-cell persistent inward current in freshly isolated hippocampal CA1 pyramidal neurons. I(Na,P) was identified by TTX-sensitivity and dependence on external Na(+) concentration. When none of the ion channels were blocked, I(Na,P) was not usually detectable, probably because competing K(+) current masked it, but after raising [K(+)](o) I(Na,P) appeared, while K(+) currents diminished. With K(+) channels blocked, I(Na,P) could usually be evoked in control solution and raising [K(+)](o) caused its reversible increase in most cells. The increase did not depend on external calcium [Ca(2+)](o). In CA1 pyramidal neurons in hippocampal slices a TTX-sensitive persistent inward current was always recorded and when [K(+)](o) was raised, it was reversibly enhanced. Strong depolarization evoked irregular current fluctuations, which were also augmented in high [K(+)](o). The findings support a role of potassium-mediated positive feedback in the generation of seizures and spreading depression.
Somjen
G G
GG
Department of Cell Biology, Box 3709, Duke University Medical Center, Durham, NC 27710, USA. g.somjen@cellbio.duke.edu
Müller
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D013181:Cortical Spreading Depression / Q000502:physiology; D004827:Epilepsy / Q000503:physiopathology; D005246:Feedback / Q000502:physiology; D006624:Hippocampus / Q000166:cytology*; D007834:Lasers; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D012640:Seizures / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium; D002118:Calcium