Long-term blockade by toxin F of nicotinic synaptic potentials in cultured sympathetic neurons.
The effects of a recently identified blocker of neuronal nicotinic transmission, toxin F, were studied in cultured sympathetic neurons. Single principal neurons, dissociated from superior cervical ganglia of newborn rats, were grown on cardiac myocytes in microculture. The toxin blocked nicotinic synaptic potentials in these cultures but had no effect on muscarinic interactions. When toxin F was applied by addition to the perfusion medium, the concentration required for blocking most of the nicotinic potential was 40 nM, and the recovery from blockade was slow (t1/2 = 95 +/- 64 min). When the toxin was briefly applied by pressure ejection from a pipette, the concentration in the pipette necessary for blockade was 21 microM, and 30-60% of the response recovered within a few minutes while the remainder recovered slowly (t1/2 of the remainder = 105 +/- 82 min). One possible explanation for the difference in recovery time is that toxin F binds initially with low affinity to the nicotinic receptor but with time the toxin receptor complex converts to a high affinity state. The presence of dihydro-beta-erythroidine during perfusion of toxin F prevented the long-lasting blockade by the toxin, suggesting that toxin F and dihydro-beta-erythroidine act through a common binding site. The specificity, potency, and slow reversibility of the effects of toxin F make it useful as a probe for studying neuronal nicotinic receptors of cultured sympathetic neurons.
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects*; D030162:Reptilian Proteins; D012910:Snake Venoms / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D009498:Neurotoxins; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D030162:Reptilian Proteins; D012910:Snake Venoms; C041907:snake venom neurotoxin F; D004079:Dihydro-beta-Erythroidine