4-Aminopyridine and dendrotoxin induce repetitive firing in rat visceral sensory neurones by blocking a slowly inactivating outward current.
In a subpopulation of rat visceral afferent neurones we have identified a potassium (K) current which is novel to mammalian neurones. It activates rapidly at potentials positive to - 70 mV but shows only slow and incomplete inactivation and is inhibited by 1-30 microM 4-aminopyridine (4-AP) or 3-10 nM dendrotoxin (DTX). Inhibition of this slowly inactivating current suppresses spike adaptation and leads to pronounced repetitive firing. In contrast, other visceral afferent neurones possessing the normal transient A-current were insensitive to 4-AP at concentrations below 100 microM. We suggest that inhibition of the slowly inactivating current may contribute to the convulsant actions of 4-AP and DTX.
C E
CE
Stansfeld
S J
SJ
Marsh
J V
JV
Halliwell
D A
DA
Brown
D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D004546:Elapid Venoms / Q000494:pharmacology*; D005724:Ganglia / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects; D009433:Neural Inhibition; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D000631:Aminopyridines; D004546:Elapid Venoms; D007473:Ion Channels; D009498:Neurotoxins; C020273:dendrotoxin; D011188:Potassium