Academic Unit: University of Nevada School of Medicine
Professional degrees (Degree, year, Institution): M.Sc., 1983, Ph.D., 1987, University of Sherbrooke, Sherbrooke, Province of Québec, Canada
Mail Stop: 318
Our research focuses on understanding the biophysical and molecular properties of ion channels in cardiac myocytes and vascular smooth muscle cells in order to define their function in health and disease. More recently, we have been mainly interested in studying the properties of Ca2+-activated Cl- channels (ClCa) in pulmonary arteries. ClCa are small conductance (~ 1-3 pS) anion channels that are considered excitatory when activated by an elevation of intracellular Ca2+ concentration above resting levels (> ~ 150 nM). Opening of ClCa causes membrane depolarization due to active transport of this anion in the cytoplasm of smooth muscle cells that leads to equilibrium potential that is ~ 25 to 30 mV more positive than the resting potential of the cells (~ -50 to -60 mV). The depolarization mediated by ClCa then in turn stimulates Ca2+ entry through voltage-gated Ca2+ channels, which increases vascular tone and causes vasoconstriction. We are presently investigating how intracellular Ca2+, membrane potential, phosphorylation (CaMKII, Calcineurin and PP1) and pharmacological agents regulate their gating mechanisms. We are also conducting projects to decipher their molecular identity and to this end are examining two candidate gene families (TMEM16 and Bestrophins) suspected to encode for these channels. Finally, recent preliminary data from our group suggest an enhanced function and/or expression of these channels in Monocrotaline model of pulmonary arterial hypertension and will soon test the hypothesis that they may represent a novel therapeutic target or marker of this disease.
Current Graduate Students
Other lab members
Abigail Forrest, Ph.D. (Research Associate)
Marissa Huebner (Undergraduate Student)
Rajesh Raghunathan (Undergraduate Student)
Michelle Van Epps (Undergraduate Student)
Sones, W. R., Leblanc, N., and I. A. Greenwood. Further investigation into the pharmacological overlap of calcium-gated chloride and potassium channels in vascular smooth muscle cells. Br J. Pharmacol. In press.
O'Driscoll KE, Hatton WJ, Burkin HR, Leblanc N and Britton FC (2008) Expression,
localization and functional properties of Bestrophin 3 channel isolated from
mouse heart. Am J Physiol Cell Physiol. 295(6):C1610-C1024.
Sun H, Varela D, Chartier D, Ruben PC, Nattel S, Zamponi GW and Leblanc
N (2008) Differential interactions of Na+ channel toxins with T-type C.a
2+ channels. J Gen Physiol 132:101-113.
Saleh SN, Angermann JE, Sones WR, Leblanc N and Greenwood IA (2007) Stimulation
of Ca2+-gated Cl- currents by the calcium-dependent K+ channel modulators
H-benzimidazol-2-one] and isopimaric acid. J Pharmacol Exp Ther 321:1075-1084.
Greenwood IA, Ledoux J, Sanguinetti A, Perrino BA and Leblanc N (2004)
Calcineurin Aa but not Ab augments ICl(Ca) in rabbit pulmonary artery smooth
muscle cells. J Biol Chem 279:38830-38837.
Ledoux J, Greenwood I, Villeneuve LR and Leblanc N (2003) Modulation of Ca2+-dependent Cl- channels by calcineurin in rabbit coronary arterial myocytes. J Physiol 552:701-714.http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12937294
Faculty by research area
- Mastick, C
- Mastick C.
- Mastick G.
- Van der Linden
- von Bartheld
- von Bartheld