Presynaptic factors in the regulation of DSI expression in hippocampus.
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.
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D063385:Cannabinoid Receptor Modulators; D026902:Potassium Channel Blockers; D011810:Quinoxalines; D017661:Receptors, Presynaptic; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015763:2-Amino-5-phosphonovalerate; D020866:omega-Conotoxin GVIA; D015761:4-Aminopyridine