Nicotine-induced depolarization of cerebral cortical synaptosomes is dependent upon sodium

Abstract

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 [ 3TPP + 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 (DMPP; 30μM) produced a small increase in the influx of 22Na + into cerebral cortical synaptosomes. The effect of DMPP on the influx of 22Na + 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.