Nickel modulation of voltage- and ligandgated ionic channels in neurons

Abstract

There is increasing evidence that toxic metals play a role in diseases of unknown etiology including neurodegenerative diseases. Nickel (Ni) is a transition metal that at high doses and in certain forms is toxic to both human and animals. Ni appears to accumulate in several organs, including the brain and, despite difficulties in its determination, concentrations ranging from 0.1 to 100 μM are consistent with those found in serum of acutely and chronically exposed human subjects. Ni neurotoxicology is largely unexplored and toxicological literature is almost restricted to Ni allergenic properties or carcinogenicity of some of its compounds. However, there are evidences that this metal affects different types of neuronal ionic channels with significant specificity. Ni blocks voltage-dependent calcium channels, being mostly effective on Cav3.2 T-type and Cav2.3 R-type, and this effect has been used to discriminate between different calcium channel types. But this metal also modulates the activity of the N-methyl-D-aspartate type of glutamate receptor channel with similar potency (μM range) and in a complex and subunit-dependent manner. In this chapter, we discuss the effect of Ni on these and other ionic channels and its potential involvement in neuronal injury.