A highly diversified group of membrane proteins shares the ability of opening ion selective pores in response to changes in the membrane voltage. My laboratory is working on several structural variants of the cardiac isoform of the dihydropyridine sensitive Ca2+ channel and a K+ channel from Caenorhabditis elegans to untersand how the coupling between the voltage sensor and pore opening is regulated.
Structure and function of the calcium channel ß-subunit. High voltage-gated calcium channels, are multi-subunit proteins complexes where a pore forming subunit combines with one or more non-homologous auxiliary subunits. One of these auxiliary subunit, is the ß-subunit.
This subunit is crucial for channel function, since it stimulate channel activity and appears to be required for surface expression of the channel protein. These two effects combined result in several fold increase in ionic current density in heterologous expression systems.

My laboratory, in collaboration with Dr. P. Hidalgo from MHH in Germany utilized purified recombinant ß-subunit combined with site directed mutagenesis to unravel how the different domain of ß-subunit regulates channel expression and function. In collaboration with Dr. Ana Maria Cardenas we are investigating the rol of the ß-subunit.

• Neely, A., X. Wei, R. Olcese, L.Birnbaumer and E. Stefani (1993). Potentiation by the ß subunit of the ratio of the ionic current to charge movement in the cardiac calcium channel. Science 262: 575-578.
• Neely A., R. Olcese, X. Wei, L. Birnbaumer and E. Stefani (1994). Calcium-dependent inactivation of cardiac calcium channels expressed in Xenopus oocytes. Biophys. J. 66: 1895-1903.
• Wei, X., A. Neely, R. Olcese, E. Stefani and L. Birnbaumer, L. (1996). Gating and ionic current from N-terminal deletions mutants of the cardiac  1 subunit. Receptors and Channels 4:205-215.
• Olcese R., A. Neely, X. Wei, L. Birnbaumer and E. Stefani (1996). Coupling Between Charge Movement and Pore Opening in Neuronal  1E Calcium Channels. J Physiol (London) 497: 675-686.
• Fleischhauer R., Wayne D.W., Dhzura I, Neely A, Avery L & Joho R.H. (2000). Ultrafast Inactivation Causes Inward Rectification in a Voltage-Gated K+ Channel from Caenorhabditis elegans. J. Neuroscience 20:1-7.
• Dhzura I., and A. Neely (2003). Modulation of cardiac Ca2+ channel opening by the  subunit. Biophys. J. 85:274-89.
• Neely A, Garcia-Olivares J, Voswinkel S, Horstkott H, Hidalgo P. (2004) Folding of active calcium channel ß1b-subunit by size-exclusion chromatography and its role on channel function. J. Biol. Chem. 279: 21689-21694.
• Hidalgo P, Gonzalez-Gutierrez G, Garcia-Olivares J, Neely A (2006). The a1-ß -subunit interaction that modulates calcium channel activity is reversible and requires a competent a-interaction domain. J. Biol. Chem. 281: 24104-24110.
• Gonzalez-Gutierrez G, Miranda-Laferte E, Neely A, Hidalgo P.(2007). The Src homology 3 domain of the ß-subunit of voltage-gated calcium channels promotes endocytosis via dynamin interaction. J. Biol. Chem. 282: 2156-2162.
• Hidalgo P. and Neely A (2007). Multiplicity of protein interactions and functions of the voltage-gated calcium channel ß-subunit. Cell Calcium. Oct-Nov;42(4-5):389-96. Review.