Presynaptic factors in the regulation of DSI expression in hippocampus

Neuropharmacology. 2002 Sep;43(4):550-62. doi: 10.1016/s0028-3908(02)00168-5.


We studied the mechanisms by which GABA release is reduced in the retrograde signaling process called depolarization-induced suppression of inhibition (DSI). DSI is mediated by endocannabinoids in acute and cultured organotypic hippocampal slices. We examined a variety of K(+) channel antagonists to determine the nature of the K(+) channel that, when blocked, reduces DSI. Among 4-AP, TEA, dendrotoxin, Cs, margatoxin, and charybdotoxin, only 4-AP was highly effective in blocking DSI, suggesting that a K(+) channel composed in part of K(V1.4,) K(V1.5) or K(V1.7) subunits can readily regulate DSI. The inhibition of DSI by 4-AP is largely overcome by reducing [Ca(2+)](o), however, suggesting that DSI expression can be prevented by saturation of the release process when a K(V1.X) channel is inhibited. DSI of agatoxin- and TTX-insensitive mIPSCs was unaffected by 4-AP, but was largely occluded by omega-conotoxin GVIA, indicating that block of presynaptic N-type Ca(2+) channels is probably a major mechanism of DSI expression. Significant DSI of mIPSCs remained in omega-conotoxin, hence we infer that block of N-channels does not fully explain hippocampal DSI expression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • 4-Aminopyridine / pharmacology
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Cannabinoid Receptor Modulators
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Hippocampus / drug effects*
  • Male
  • Membrane Potentials / physiology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Presynaptic / drug effects*
  • Signal Transduction / drug effects*
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology
  • omega-Conotoxin GVIA / pharmacology


  • Calcium Channel Blockers
  • Cannabinoid Receptor Modulators
  • Potassium Channel Blockers
  • Quinoxalines
  • Receptors, Presynaptic
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Tetrodotoxin
  • Tetraethylammonium
  • 2-Amino-5-phosphonovalerate
  • omega-Conotoxin GVIA
  • 4-Aminopyridine