Modulation of synaptic transmission in hippocampal CA1 neurons by a novel neurotoxin (beta-pompilidotoxin) derived from wasp venom.
We examined the effects of beta-pompilidotoxin (beta-PMTX), a neurotoxin derived from wasp venom, on synaptic transmission in the mammalian central nervous system (CNS). Using hippocampal slice preparations of rodents, we made both extracellular and intracellular recordings from the CA1 pyramidal neurons in response to stimulation of the Schaffer collateral/commissural fibers. Application of 5-10 microM beta-PMTX enhanced excitatory postsynaptic potentials (EPSPs) but suppressed the fast component of the inhibitory postsynaptic potentials (IPSPs). In the presence of 10 microM bicuculline, beta-PMTX potentiated EPSPs that were composed of both non-NMDA and NMDA receptor-mediated potentials. Potentiation of EPSPs was originated by repetitive firings of the presynaptic axons, causing summation of EPSPs. In the presence of 10 microM CNQX and 50 microM APV, beta-PMTX suppressed GABA(A) receptor-mediated fast IPSPs but retained GABA(B) receptor-mediated slow IPSPs. Our results suggest that beta-PMTX facilitates excitatory synaptic transmission by a presynaptic mechanism and that it causes overexcitation followed by block of the activity of some population of interneurons which regulate the activity of GABA(A) receptors.
Yokota
H
H
Department of Surgical Neurology, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan. yokota-h@jichi.ac.jp
Tsubokawa
H
H
Miyawaki
T
T
Konno
K
K
Nakayama
H
H
Masuzawa
T
T
Kawai
N
N
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D019476:Insect Proteins; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D010721:Phosphinic Acids / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D015222:Sodium Channels / Q000145:classification / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014862:Wasp Venoms / Q000737:chemistry*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D019476:Insect Proteins; D009498:Neurotoxins; D010721:Phosphinic Acids; D011412:Propanolamines; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D014862:Wasp Venoms; C115329:pompilidotoxin beta; C085075:CGP 55845A; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; C006749:bicuculline methochloride; D001640:Bicuculline