|Professor of Biology
Cellular and molecular physiology of ion channels
Dr. Yoshikami's work is focused on the cellular and molecular physiology of voltage-gated and ligand-gated ion channels. In collaboration with Professors B.M. Olivera and J.M. McIntosh, he is identifying and characterizing the ion channel-targets of a variety of neuroactive peptides (the conotoxins). These peptides can block specific subtypes of ligand-gated channels (e.g., acetylcholine or glutamate receptors) while others target specific isoforms of voltage-gated sodium, calcium or potassium channels. The detailed pharmacology of the conotoxins is being studied using endogenous ion channels in dissociated neurons and cloned ion channels expressed in Xenopus oocytes or mammalian cell lines. He is also using the conotoxins to probe the functional roles of given isoforms of ion channels in intact, isolated tissue preparations. For example, he is examining the involvement of various sodium channels in nociception with recently discovered u-conotoxins that blocks these channels.
Zhang, M.M., Gruszczynski, P., Walewska, A., Bulaj, G., Olivera, B.M., and Yoshikami, D. (2010) Co-occupancy of the Outer Vestibule of Voltage-gated Sodium Channels by mu-Conotoxin KIIIA and Saxitoxin or Tetrodotoxin. J Neurophysiol, 104: 88-97.
Zhang, M.M., Han, T.S., Olivera, B.M., Bulaj, G., and Yoshikami, D. (2010) Mu-conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channels. Biochemistry, 49:4804-4812.
Zhang, M.M., McArthur, J.R., Azam, L., Bulaj, G., Olivera, B.M., French, R.J., and Yoshikami, D. (2009) Synergistic and antagonistic interactions between tetrodotoxin and μ-conotoxin in blocking voltage-gated sodium channels. Channels, 3:32-38.
Walewska, A., Zhang, M.M., Skalicky, J.J., Yoshikami, D., Olivera, B.M., and Bulaj, G. (2009) Integrated oxidative folding of cysteine/selenocysteine containing peptides: improving chemical synthesis of conotoxins. Angew Chem Int Ed Engl, 48:2221-2224.
Khoo, K.K., Feng, Z.P., Smith, B.J., Zhang, M.M., Yoshikami, D., Olivera, B.M., Bulaj, G., and Norton, R.S. (2009) Structure of the analgesic μ-conotoxin KIIIA and effects on structure and function of disulfide deletion. Biochemistry, 48:1210-1219.
Holford, M., Zhang, M.M., Gowd, K.H., Azam, L., Green, B.R., Watkins, M., Ownby, J.P., Yoshikami, D., Bulaj, G., and Olivera, B.M. (2009) Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon, 53:90-98.
Han, T.S., Zhang, M.M., Walewska, A., Gruszczynski, P., Robertson, C.R., Cheatham 3rd, T.E., Yoshikami, D., Olivera, B.M., and Bulaj, G. (2009) Structurally Minimized mu-Conotoxin Analogues as Sodium Channel Blockers: Implications for Designing Conopeptide-Based Therapeutics. ChemMedChem, 4:406-414.
Fiedler, B., Zhang, M.M., Buczek, O., Azam, L., Bulaj, G., Norton, R.S., Olivera, B.M., and Yoshikami, D. (2008) Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of voltage-gated sodium channels NaV1.2, 1.6 and 1.7. Biochemical pharmacology, 75:2334-2344.
Azam, L., Yoshikami, D., and McIntosh, J.M. (2008) Amino acid residues that confer high selectivity of the alpha6 nicotinic acetylcholine receptor subunit to alpha-conotoxin MII[S4A,E11A,L15A]. The Journal of biological chemistry, 283:11625-11632.
Buczek, O., Jimenez, E.C., Yoshikami, D., Imperial, J.S., Watkins, M., Morrison, A., and Olivera, B.M. (2008) I1-superfamily conotoxins and prediction of single D-amino acid occurrence. Toxicon, 51:218-229.
Meyer, E.L., Yoshikami, D., and McIntosh, J.M. (2008) The neuronal nicotinic acetylcholine receptors alpha 4* and alpha 6* differentially modulate dopamine release in mouse striatal slices. Journal of neurochemistry, 105:1761-1769.
Walewska, A., Skalicky, J.J., Davis, D.R., Zhang, M M., Lopez-Vera, E., Watkins, M., Han, T.S., Yoshikami, D., Olivera, B.M., and Bulaj, G. (2008) NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA. Journal of the American Chemical Society, 130:14280-14286.
Yao, S., Zhang, M.M., Yoshikami, D., Azam, L., Olivera, B.M., Bulaj, G., and Norton, R.S. (2008) Structure, dynamics, and selectivity of the sodium channel blocker mu-conotoxin SIIIA. Biochemistry, 47:10940-10949.
Bulaj, G., Zhang, M.M., Green, B.R., Fiedler, B., Layer, R.T., Wei, S., Nielsen, J.S., Low, S.J., Klein, B.D., Wagstaff, J.D., Chicoine, L., Harty, T.P., Terlau, H., Yoshikami, D., and Olivera, B.M. (2006) Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity. Biochemistry, 45:7404-7414.
Zhang, M.M., Fiedler, B., Green, B.R., Catlin, P., Watkins, M., Garrett, J.E., Smith, B.J., Yoshikami, D., Olivera, B.M., and Bulaj, G. (2006) Structural and functional diversities among mu-conotoxins targeting TTX-resistant sodium channels. Biochemistry, 45:3723-3732.
Buczek, O., Yoshikami, D., Bulaj, G., Jimenez, E.C., and Olivera, B.M. (2005) Post-translational amino acid isomerization: a functionally important D-amino acid in an excitatory peptide. The Journal of Biological Chemistry, 280:4247-4253.
West, P.J., Bulaj, G., and Yoshikami, D. (2005) Effects of delta-conotoxins PVIA and SVIE on sodium channels in the amphibian sympathetic nervous system. Journal of Neurophysiology, 94:3916-3924.