Nicotine-induced depolarization of cerebral cortical synaptosomes is dependent upon sodium.
Earlier studies from this laboratory demonstrated that activation of nicotinic cholinergic receptors of cerebral cortical synaptosomes of the rat produced a decrease in the accumulation of [3H]tetraphenylphosphonium ([3H]TPP+) as a result of a decreased synaptosomal membrane potential. In the present study, the role of sodium in the effect of nicotine on the accumulation of [3H]TPP+ and the estimated potential difference was explored. Replacement of buffer sodium with either sucrose or N-methyl-D-glucamine (NMDG), attenuated the depolarization produced by the sodium channel activator, veratridine and had no effect on potassium-induced depolarization. The effect of nicotine on accumulation of [3H]TPP+ into cerebral cortical synaptosomes was abolished in sucrose buffer and attenuated in NMDG buffer. 1,1-Dimethyl-4-phenylpiperazinium iodide (DMP; 30 microM) produced a small increase in the influx of 22Na+ into cerebral cortical synaptosomes. The effect of DMPP on the influx of 22 Na+ was not blocked by tetrodotoxin. These results support the hypothesis that the nicotinic cholinergic receptor in the brain, functions as a sodium ionophore and further demonstrate that accumulation of synaptosomal [3H]TPP+ provides a simple tool with which to assess the effect of nicotine on sodium permeability through open nicotinic cholinergic receptor ionophores.
Hillard
C J
CJ
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D009861:Onium Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects; D012964:Sodium / Q000502:physiology*; D012979:Sodium Radioisotopes; D013574:Synaptosomes / Q000187:drug effects*; D014701:Veratridine / Q000494:pharmacology
D000970:Antineoplastic Agents; D009467:Neuromuscular Depolarizing Agents; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D011950:Receptors, Cholinergic; D012979:Sodium Radioisotopes; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D014701:Veratridine; D012964:Sodium; D011188:Potassium; C013289:tetraphenylphosphonium