Investigation of mechanism of central nervous system disorder due to chlorinated

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Calcium ion in neurons plays an important role in development of action potential, release of neurotransmitter and intracellular signaling with synapse formation and physiological functions. Intracellular calcium ion is derived from either influx from the extracellular fluid through the membrane calcium channels o* release out of the intracellular calcium store sites. Organic solvents used in the field of manufacturing and service industry cause clinical symptoms related to depression of central nervous system function.We have dissociated dorsal root ganglion neurons from neonatal rat to measure the voltage-dependent calcium current in a whole cell mode of the patch clump. Trichloroethane and trichloroethyene decreased the calcium current. And intervals of the action potential in the current clump mode were shortened. We also found the involvement of other voltage-gated cation channels. Next we investigated the change of intracellular calcium ion concentration released from the intracelular calcium stores with a fluo-indicator Fluo-3. We used in this experiments caffeine which modifies ryanodine receptor of intracellular calcium store, and ATP which stimulates the nucleotide receptor of the DRG neurons. Caffeine induced the increasing of the intracellular calcium level, and trichloroethylene inhibited the increasing. The rise of the intracellular calcium level was also impaired with 1-bromopropane and 2-bromopropane. We also studied aortic smooth muscle and got the same results. These studies suggested that some of organic solvents could act on both the plasma membrane of the neurons and cytoplasmic organelles in entering though the plasma membrane and finally modify the action potential and neurotransmitter release.