Normand Leblanc

Contact Information:

Normand Leblanc, Ph.D.

Professor of Pharmacology/MS 318

Director of the High Spatial and Temporal Imaging Core

Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System

Associate Editor, Frontiers in Physiology, Vascular Physiology section

University of Nevada, Reno School of Medicine

Manville Health Sciences Building, Room 9D

1664 North Virginia St.

Reno, Nevada 89557-0318

 

Phone: (775) 784-1420

Cell: (775) 741-1645

Fax: (775) 784-1620

Email: nleblanc@unr.edu

Peer-Reviewed Publications: 89; cited 4350; h-index: 36; i10 index: 63; Data from Google Scholar as of 10/04/2023.

Complete List of Published Work in My Bibliography:

https://www.ncbi.nlm.nih.gov/myncbi/normand.leblanc.1/bibliography/public/

Research Interests:

 

  • Role of ion channels in excitation-contraction coupling of vascular smooth muscle cells.
  • Biophysical properties, regulation, and function of Ca2+-activated Cl- channels encoded by the gene TMEM16A (Anoctamin-1 or ANO1) in pulmonary hypertension.
  • Investigation of the effects of ultrashort (5 ns) high intensity electric pulses (NEPs) on the electrophysiological properties, Ca2+ dynamics and neurosecretory properties of adrenal chromaffin cells with the long-term goal of developing non-invasive electrostimulation techniques (e.g., a soldier-worn “wearable” antenna system) that could rapidly enhance the adrenal “flight or fight” response in warfighters as a way to augment human performance.
  • Study of functional trade-offs that govern adaptation and coevolutionary dynamics of voltage-gated Na+ channels in the predator-prey relationship between Sierra Nevada garter snakes (Thamnophis spp.) and toxic newts (Taricha spp.).

Education:

     

    • Sc. in Biology, University of Sherbrooke, Québec, Canada, 1981
    • Sc. in Biophysics, University of Sherbrooke, Québec, Canada, 1983
    • D. in Biophysics, University of Sherbrooke, Québec, Canada, 1987
    • Post-doctoral fellow, Department of Pharmacology, Michigan State University, 1987
    • Post-doctoral fellow, Department of Physiology, University of Nevada, Reno, 1987-1990

     

    Biography:

     

    Dr. Leblanc is a well-trained biophysicist with broad knowledge in Physiology and Pharmacology, and a specific expertise in cardiac, smooth, and skeletal muscle electrophysiology (extracellular and intracellular recording techniques, patch clamp) as well as neuronal electrophysiology, quantitative fluorescence imaging (standard epifluorescence, confocal microscopy, TIRFM, super resolution microscopy), force measurements in multicellular preparations, and computer modeling of ion channel gating.

    During his graduate training, Dr. Leblanc learned basic concepts related to electrophysiology and ion channels. He became familiarized with intracellular recording techniques to measure action potentials in rapidly beating Langendorff-perfused rabbit ventricles and atria using floating glass microelectrodes. The major aim of his project during his Master’s and Ph.D. degrees was to determine the ionic basis of the resting membrane potential and action potential in hypoxic myocardium.  His results allowed him to conclude that in hypoxia: 1) a large increase in K+ permeability is responsible for maintaining the resting potential of ventricular muscle cells in spite of a net loss of intracellular K+; the reduced PNa/PK attenuated a contribution of the electrogenic Na+-K+ pump to the resting membrane potential due to reduced membrane resistance; and 2) ventricular action potential shortening is multifactorial involving activation of K+ channels and an unidentified outward conductance near the plateau of the action potential, which can be amplified or attenuated by changing the intracellular Na+ and Ca2+ loads.

    Dr. Leblanc’s early work as a post-doctoral fellow and then as a junior independent investigator led his collaborative team to propose a novel concept in cardiac excitation-contraction coupling (EC-coupling). They reported for the first time (paper published in Science) that fast tetrodotoxin-sensitive voltage-gated Na+ channels responsible for the upstroke of the ventricular action potential can induce release of calcium from the sarcoplasmic reticulum by a mechanism that involves reverse mode activity (Ca2+ influx) from electrogenic Na+/Ca2+ exchange activity triggered by a subsarcolemmal elevation in intracellular Na+ concentration.

    Work also initiated as a post-doctoral fellow continued as an independent investigator involved seminal investigations characterizing the biophysical properties of voltage-gated K+ and Ca2+ channels in rabbit portal vein and coronary artery smooth muscle cells.  These studies described the important role played by delayed rectifier (Kv) and large conductance Ca2+-activated K+ channels (BK) in determining resting membrane potential and vascular tone, their pharmacology, how local Ca2+ entry through L-type Ca2+ channels, Ca2+ release from the sarcoplasmic reticulum, regulation by metabolic inhibition regulate BK channels.

    Work initiated in Dr. Leblanc’s lab in the mid 1990’s and still ongoing today has made a strong argument for an important role of Ca2+-activated Cl- channels (CaCCs) in determining membrane potential, Ca2+ dynamics and vascular tone in many important vascular beds.  They also provided evidence that CaCCs are functionally down-regulated by at least one phosphorylation step involving Ca2+/Calmodulin-dependent kinase II, a process that is antagonized by the serine-threonine phosphatases Calcineurin, PP1 and PP2A. More recently, their studies showed that CaCCs are also regulated by the membrane phospholipid PIP2, and that the recently discovered gene Tmem16A or Anoctamin1 now known to encode for CaCCs is highly expressed in vascular myocytes and is up regulated in pulmonary hypertension.

    In 2012, Dr. Leblanc became involved in a new collaborative project with one of another faculty in the Department of Pharmacology, Dr. Gale L. Craviso, examining the effects of ultrashort (5 ns) high intensity electric pulses (NEP) on the electrical properties and excitation-secretion coupling of bovine chromaffin cells. The main goal of this project funded by the Air Force of Scientific Research (AFOSR) is to develop non-invasive electrostimulation techniques (e.g., a soldier-worn “wearable” antenna system) that could rapidly enhance the adrenal “flight or fight” response in warfighters as a way to augment human performance.  Their data have so far indicated that a single 5 ns NEP at 5 MV/m can elicit a non-selective cation conductance and is able to alter the properties of voltage-gated Na+ channels. Moreover, application of bipolar nanosecond pulses can cancel response, a modality that could be used for improved spatial targeted electrostimulation.

    In 2013, Dr. Leblanc began to collaborate with Dr. Chris Feldman, Associate Professor of Biology at UNR, on a project funded by the NSF examining the evolution of voltage-gated Na+ channels in garter snakes that have coevolved with toxic newts in the Sierra Nevada Mountain range.  The newts secrete the neurotoxin tetrodotoxin (TTX) through their skin.  Dr. Feldman’s team previously identified several species of garter snakes that are extremely insensitive to TTX and can thus prey on these toxic newts without negative consequences.  Analysis of the amino acid composition of the Na+ channel pore where TTX binds to, and blocks this channel, revealed a number of mutations that dramatically reduces the affinity of TTX on this channel. The collaborative project with Dr. Leblanc’s team tested the hypothesis that these mutations may impact at the organismal level.  They found that the skeletal muscles of two species of garter snake exhibiting extreme insensitivity to TTX were weaker than “wild type” snakes lacking these mutations, which was interpreted as a functional trade-off, which may explain locomotor deficits observed in resistant snakes and variation in the population-level success of toxin-resistant alleles across the landscape.

     

    Selected Citations:

     

    1. Leblanc, N., and J.R. Hume. 1990. Sodium current-induced release of calcium from cardiac sarcoplasmic reticulum. Science. 248:372-376.
    2. Forrest, A.S., T.C. Joyce, M.L. Huebner, R.J. Ayon, M. Wiwchar, J. Joyce, N. Freitas, A.J. Davis, L. Ye, D.D. Duan, C.A. Singer, M.L. Valencik, I.A. Greenwood, and N. Leblanc. 2012. Increased TMEM16A-encoded calcium-activated chloride channel activity is associated with pulmonary hypertension. Am J Physiol Cell Physiol. 303:C1229-C1243.
    3. Yang, L., S. Pierce, T.W. Gould, G.L. Craviso, and N. Leblanc. 2022. Ultrashort nanosecond electric pulses activate a conductance in bovine adrenal chromaffin cells that involves cation entry through TRPC and NALCN channels. Arch Biochem Biophys. 723:109252.
    4. Akin, E.J., J. Aoun, C. Jimenez, K. Mayne, J. Baeck, M.D. Young, B. Sullivan, K.M. Sanders, S.M. Ward, S. Bulley, J.H. Jaggar, S. Earley, I.A. Greenwood, and N. Leblanc. 2023. ANO1, CaV2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle. J Gen Physiol., 155.