Associate Professor - Department of Neuroscience Associate Professor - Department of Molecular Physiology and Biophysics Ph.D., University of Washington, 1987 One Baylor Plaza Baylor College of Medicine Houston TX, 77030 Telephone: 713-798-3060 - Fax: 713-798-3946 Email: paulp@bcm.edu

A fundamental question in neuroscience is how genetic regulation of neuronal electrophysiological properties acts to produce the variety of electrical phenotypes in the brain. A primary concern in addressing this question is to identify the native ion channels that are formed from specific genes in order to understand how regulation of these genes translates into changes in cellular electrophysiological properties. Gene cloning and expression studies have identified many genes that likely express proteins that form ion channels alpha subunits, or make auxiliary proteins that modulate the function of pore forming alpha subunits. Neurophysiological studies have identified numerous current components in neurons based on different biophysical and pharmacological properties. The problem then is how to best link specific gene transcripts with the formation of a specific native neuronal ion channel. Our research project are examining the composition of native voltage gated potassium channels using a variety of molecular and biophysical approaches. We are identifying the combination of pore forming and auxiliary subunits that are required for form specific native ion channels. Our studies are revealing how modifications in subunit composition produces a variety of functionally distinct ion channel proteins, through differential gene expression, alternative splicing and post-translational modifications. In addition to identifying and characterizing the composition of native ion channels, we are also interested in structure function studies aimed at determining how these protein composition changes produce their functional effects. Ours studies have examined the specific structural basis for the binding interactions between subunits, the structural and functional basis for changes in channel functional properties, as well as the structural and functional basis for changes in protein expression and targeting in native neurons. Our research has important implications for understanding the fundamental processes involved in learning and memory as well as the disease processes associated with aberrant neuronal function such as epilepsy and other movement and thought disorders.

top

Strang, C., Kunjilwar, K., DeRubeis, D., Peterson, D., and Pfaffinger, P.J. (2003). The role of Zn2+ in Shal voltage-gated potassium channel formation. J. Biol. Chem. 278 (33): 31361-31371.

Zhou, W, Qian, Y, Kunjilwar, K., Pfaffinger, P.J. and Choe, S. (2004). Structural insights into the Functional Interaction of KChIP1 with Shal-type K+ channels. Neuron 41: 573-586.

Jerng, H.H., Qain, Y., and Pfaffinger, P.J. (2004) Modulation of Kv4.2 Channel Expression and Gating by Dipeptidyl Peptidase 10 (DPP10). Biophysics J. 87: 2380-2396.

Kunjilwar, K., Strang, C., DeRubeis, D., and Pfaffinger, P.J. (2004). KChIP3 Rescues the Functional Expression of Shal Channel Tetramerization Mutants. J Biol Chem, 279(52): 54542-51

Wang, G., Shahidullah, M., Rocha, C.A., Strang, C., Pfaffinger, P.J., Covarrubias, M. (2005). Functionally active t1-t1 interfaces revealed by the accessibility of intracellular thiolate groups in Kv4 channels. J Gen Physiol. 126(1):55-69.

Jerng, H.H., Kunjilwar, K, Pfaffinger, P.J. (2005). Multiprotein Assembly of Kv4.2, KChIP3, and DPP10 Produces Ternary Channel Complexes with ISA-like Properties. J Physiol. 568: 767-785.

Baker, K.A., Hilty, C., Peti, W., Prince, A., Pfaffinger, P.J., Wider, G., Wuthrich, K., and Choe, S. (2006). NMR-derived dynamic aspects of N-type inactivation of a Kv channel suggest a transient interaction with the T1 domain. Biochemistry 45:1663-1672.

Lauver,A., Yuan, L., Jeromin, A., Nadin, B.M.,Rodriguez, J.J., Davies, H.A., Stewart, M.G., Wu, G.Y., and Pfaffinger, P.J. (2006). Manipulating Kv4.2 Expression Identifies a Specific Component of Hippocampal Pyramidal Neuron A Current that Depends Upon Kv4.2 Expression. J. Neurochemistry, 99, 1207-1223.

Guangyu Wang, Candace Strang, Paul J. Pfaffinger and Manuel Covarrubias (2007). Zn2+-Dependent Redox Switch in the Intracellular T1-T1 Interface of a Kv Channel. J. Biol. Chem. 282(18):13637-47.

Henry H. Jerng, Aaron D. Lauver, and Paul J. Pfaffinger (2007). DPP10 splice variants are localized in distinct neuronal populations and act to differentially regulate the inactivation properties of Kv4-based ion channels. Mol. Cell. Neurosci. 35(4): 604-625.

top

Klingenstein Fellowship Award in Neuroscience

American Heart Association-Established Investigator Award

Graduate Student Admission Cmte, Chairman (2005)

Graduate Program Associate Director

Member Board of Directors for BraesBayou and West University Little Leagues

Marc Dresden Award for Excellence in Graduate Education (2007)

top

• Brian Nadin (Neuroscience)

top

RNA Interference identifies Kv4.2 as the gene responsible for A current in hippocampal pyramidal neurons. A) We developed an RNA interference vector pSuperRed that knocks down specific genes while labeling transfected neurons with a red fluorescent protein. B) Transfection with pSuperRed knocks down the expression of a specific gene in a red labeled hippocampal pyramidal neuron. C) Targeting vector for Kv4.2 gene suppresses Kv4.2 protein expression. D) Knockdown of Kv4.2 expression suppresses A type current by over 60% in 2 days.

top