We are interested in molecular interactions of the pore-forming region of the NaV channel that determines ionic selectivity for Na+ vs. other inorganic cations such as K+ and Ca2+. A cluster of charged residues called the "DEKA locus" has been shown to be important for a number of key channel properties such as: discrimination among inorganic cations, exclusion of divalent inorganic cations, and molecular sieving of organic cations. We discovered that intracellular polyamines such as spermine and spermidine, act as blockers and gating modulators of the rat muscle NaV channel. We have recently extended this work to examine polyamine interactions with other gene isoforms of NaV channels with a view toward using polyamine block as a probe of the permeation pathway and gating mechanism. We are also involved in purifying neuroactive peptides from venoms of various species of Chinese bird spiders and marine Cone snails in an attempt to discover new toxins that might be useful as pharmacological tools and drug leads.

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