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.