Differential modulation of TTX-sensitive and TTX-resistant Na+ channels in spinal cord astrocytes following activation of protein kinase C

C. L. Thio, H. Sontheimer

Research output: Contribution to journalArticlepeer-review

Abstract

TTX-sensitive (TTX-S) and TTX-resistant (TTX-R) Na+ currents are expressed in high densities (2-8 channels/μm2) in astrocytes cultured from neonatal rat spinal cord. The two Na+ current types differ up to 1000-fold in their TTX sensitivity and additionally have different steady-state activation (g-V) and inactivation (h(∞)) curves. Expression of TTX-S and TTX-R Na+ currents is confined to morphologically distinguishable subtypes of astrocytes, allowing characterization of the two types of Na+ currents in isolation: stellate cells express TTX-S Na+ currents and flat pancake cells express TTX-R Na+ currents. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) exhibited different effects on TTX-S and TTX-R Na+ currents. PMA reduced peak TTX-S Na+ currents by 25-60%; in contrast, PMA potentiated peak TTX-R Na+ currents by 60-150%. These effects developed within minutes, and were typically not reversible. PMA effects were voltage dependent, and shifted steady-state Na+ current activation of TTX-R and TTX- S currents by 6 and 18 mV, respectively, but without affecting their steady- state current inactivation (h(∞)). PMA treatment also changed Na+ current kinetics. TTX-R current activation (τ(m)) was faster and current inactivation (τ(h)) changed from a single- to a bi-exponential after PMA exposure, suggesting that PKC phosphorylation may have activated formerly quiescent Na+ channels. In contrast, TTX-S current activation (τ(m)) was unchanged, and current inactivation (τ(h)), on average, decreased by 50% following PMA exposure. Since these effects of PMA could be reduced or abolished by the PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2- methylpiperazine (H7), it is concluded that PMA effects were mediated by activation of PKC.

Original languageEnglish (US)
Pages (from-to)4889-4897
Number of pages9
JournalJournal of Neuroscience
Volume13
Issue number11
DOIs
StatePublished - 1993
Externally publishedYes

Keywords

  • Na channel
  • TTX
  • astrocyte
  • patch clamp
  • phorbol ester
  • protein kinase C

ASJC Scopus subject areas

  • Neuroscience(all)

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