Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input

M. Tanaka, T. R. Cummins, K. Ishikawa, J. A. Black, Y. Ibata, S. G. Waxman

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Neurons respond to stimuli by integrating generator and synaptic potentials and generating action potentials. However, whether the underlying electrogenic machinery within neurons itself changes, in response to alterations in input, is not known. To determine whether there are changes in Na+ channel expression and function within neurons in response to altered input, we exposed magnocellular neurosecretory cells (MNCs) in the rat supraoptic nucleus to different osmotic milieus by salt-loading and studied Na+ channel mRNA and protein, and Na+ currents, in these cells. In situ hybridization demonstrated significantly increased mRNA levels for α-II, Na6, β1 and β2 Na+ channel subunits, and immunohistochemistry/immunoblotting showed increased Na+ channel protein after salt-loading. Using patch-clamp recordings to examine the deployment of functional Na+ channels in the membranes of MNCs, we observed an increase in the amplitude of the transient Na+ current after salt-loading and an even greater increase in amplitude and density of the persistent Na+ current evoked at subthreshold potentials by slow ramp depolarizations. These results demonstrate that MNCs respond to salt-loading by selectively synthesizing additional, functional Na+ channel subtypes whose deployment in the membrane changes its electrogenic properties. Thus, neurons may respond to changes in their input not only by producing different patterns of electrical activity, but also by remodeling the electrogenic machinery that underlies this activity.

Original languageEnglish (US)
Pages (from-to)1088-1093
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number3
DOIs
StatePublished - Feb 2 1999
Externally publishedYes

Keywords

  • Electrogenesis
  • Gene transcription
  • Ion channels
  • Sodium channels

ASJC Scopus subject areas

  • General

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