The applicant for this K01, """"""""Career Development Award for Minority Scholars in Neuroscience"""""""" is Prosper N'Gouemo, Ph.D., an Assistant Professor in the Department of Pharmacology, Georgetown University Medical School. The applicant's short-term goals are to obtain additional training in calcium (Ca) imaging, single cell RNA amplification, electrophysiology of glutamate- and acetylcholine nicotinic-evoked currents, while increasing his training in Ca and potassium (K) channels, and epilepsy. The applicant's long-term objectives are to acquire additional skills as to make him an effective and independent investigator in neurosciences. Dr. M. Morad, a well known researcher in the field of ion channels, will serve as mentor. Additional specialized co-mentors, consultants, and collaborator in electrophysiology, molecular biology, and epilepsy will actively participate in the applicant's career development. The overall objective of this research project is to identify potential mechanisms that account for the upregulation of high threshold voltage activated Ca and downregulation of Ca-activated K current density in inferior colliculus (IC) neurons of genetically epilepsy-prone rat (GEPR), an inherited model of generalized tonic/clonic epilepsy. The central hypothesis to be tested is that upregulation of Ca and downregulation of K currents contribute to IC neuronal hyperexcitability that predisposes the GEPR to seizures. To test this hypothesis, the following specific aims are proposed: 1) Determine which Ca channel type accounts for the upregulation of Ca currents; 2) Determine whether changes in current activation/inactivation parameters and phosphorylation state of Ca channel via protein kinase A and C account for increases in Ca currents; 3) Determine whether Ca release from internal sources is altered in the GEPR; 4) Determine which component of Ca-activated K channels accounts for downregulation of Ca-activated K currents; 5) Determine whether the sensitivity of K channels to Ca is altered in the GEPR; 6) Determine whether changes in the levels of expression of Ca and Ca activated K channel mRNA and proteins occur in IC neurons of the GEPR. The results of these studies may lead to an improved understanding of the role of Ca and Ca-activated K channels in neuronal hyperexcitability that leads to seizure susceptibility and epilepsy as well as shed light to identify potentially novel molecular target for the therapy of generalized tonic/clonic epilepsy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NS047193-04
Application #
7414064
Study Section
NST-2 Subcommittee (NST)
Program Officer
Fureman, Brandy E
Project Start
2005-05-18
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
4
Fiscal Year
2008
Total Cost
$172,422
Indirect Cost
Name
Georgetown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Quansah, Hillary; N'Gouemo, Prosper (2014) Amiloride and SN-6 suppress audiogenic seizure susceptibility in genetically epilepsy-prone rats. CNS Neurosci Ther 20:860-6
N'Gouemo, Prosper; Morad, Martin (2014) Alcohol withdrawal is associated with a downregulation of large-conductance Ca²?-activated K? channels in rat inferior colliculus neurons. Psychopharmacology (Berl) 231:2009-18
N'Gouemo, Prosper (2013) Probing the role of the sodium/calcium exchanger in pentylenetetrazole-induced generalized seizures in rats. Brain Res Bull 90:52-7
N'Gouemo, Prosper (2011) Targeting BK (big potassium) channels in epilepsy. Expert Opin Ther Targets 15:1283-95
Martinez, Yuris; N'Gouemo, Prosper (2010) Blockade of the sodium calcium exchanger exhibits anticonvulsant activity in a pilocarpine model of acute seizures in rats. Brain Res 1366:211-6
N'Gouemo, Prosper; Yasuda, Robert; Faingold, Carl L (2010) Seizure susceptibility is associated with altered protein expression of voltage-gated calcium channel subunits in inferior colliculus neurons of the genetically epilepsy-prone rat. Brain Res 1308:153-7
N'gouemo, Prosper; Faingold, Carl L; Morad, Martin (2009) Calcium channel dysfunction in inferior colliculus neurons of the genetically epilepsy-prone rat. Neuropharmacology 56:665-75
N'Gouemo, Prosper; Yasuda, Robert P; Faingold, Carl L (2009) Protein expression of small conductance calcium-activated potassium channels is altered in inferior colliculus neurons of the genetically epilepsy-prone rat. Brain Res 1270:107-11
N'Gouemo, Prosper (2008) Amiloride delays the onset of pilocarpine-induced seizures in rats. Brain Res 1222:230-2
N'Gouemo, Prosper; Yasuda, Robert P; Morad, Martin (2006) Ethanol withdrawal is accompanied by downregulation of calcium channel alpha 1B subunit in rat inferior colliculus neurons. Brain Res 1108:216-20