Robert Brenner, Ph.D.
Cellular and Integrative Physiology
The focus of Dr. Robert Brenner's lab has been to understand how ion channels regulate excitability of cells. Our approach is to use electrophysiology and biophysical techniques to understand channel regulation in vitro, and complement these studies by generating mouse models to understand the physiological consequences of ion channel regulation.
Currently, our lab is investigating the role of the large conductance calcium- and voltage-activated potassium channel and their accessory beta subunits in regulating excitability in hippocampal neurons (brain slice preparation, calcium measurements, and EEG recordings) and in airway smooth muscle (muscle constriction studies and electrophysiology).
We have made major contributions to understanding this ion channel, from early characterization of the Drosophila gene where it was first cloned, to initial cloning and characterization of the accessory subunits, to gene knockout of accessory beta1 and beta4 subunits in mice. The biophysical studies in our lab have provided new incite into how beta subunits modulate BK channel gating. Recent contributions from our lab include findings that BK potassium channel gain-of-function enhance excitability in some neurons to promote seizures and epilepsy.
We are currently studying how BK channels are regulated by functional coupling with colocalized calcium sources in dentate gyrus granule neurons and airway smooth muscle.
- 1997 - PhD - Biology - University of Texas at Austin
- 1992 - MS - Biology - San Diego State University
- 1982 - BS - Microbiology - University of Texas at Arlington
- Postdoctoral Fellowship - Biology - Stanford University School of Medicine
- 9/2008 - Associate Professor - University of Texas Health Science Center, Physiology, San Antonio
Instruction & Training
- 9/2011 - Present, Fundamentals of Biomedical Sciences, The University of Texas Health Science Center
- 3/2009 - Present, Pre-Doctoral Student Supervision, UT Health Science Center San Antonio
- 1/2006 - Present, Dental Physiology, The University of Texas Health Science Center
- 1/2005 - Present, Mammalian Physiology, The University of Texas Health Science Center
- 1/2004 - Present, Rotation Student Supervision, UTHSCSA
- 1/2004 - Present, UTHSCSA
- 6/2003 - Present, Post-Doctoral Student Supervision, UT Health Science Center San Antonio
- 1/2003 - Present, Membership on Supervising Committee, University of Texas Health Science Center
Research & Grants
We wish to apply our studies of ion channels to two broad areas of research. One area is to understand adaptive and maladaptive changes in excitability in the brain, that occur as a result of seizures and traumatic brain injury. We utilize brain slice patch clamp electrophysiology, and video-EEG monitoring of mice, to understand how trauma results in seizures and post-traumatic epilepsy.
Related diseases: Epilepsy, Asthma
Techniques: Patch clamp electrophysiology, transgenic and knockout mice, isometric contractions studies, confocal imaging, molecular biology
Bugay V, Kurbanov EB, Vigil FAB, Chun SH, Holstein DM, Elliot R, Sprague C, Rule G, Cavazos JE, Zamora D, Shapiro MS, Lechleiter JD, Brenner R, A mouse model of repetitive blast traumatic brain injury reveals acute seizures and increased neuronal excitability, 2019, Journal of Neurotrauma, 2019, in press.
Lee B, Lee K, Panda S, Gonzales-Rojas R, Chong A, Bugay V, Park HM, Brenner R, Murthy N, Lee HY, Nanoparticle delivery of CRISPR into the brain rescues a mouse model of fragile X syndrome from exaggerated repetitive behaviours, Nature Biomedical Engineering, 2018, 2018 Jul;2(7):497-507.
Semenov I, Brenner R. Voltage effects on muscarinic acetylcholine receptor-mediated contractions of airway smooth muscle. Physiol Rep. 2018 Sep;6(17):e13856. doi: 10.14814/phy2.13856. PubMed PMID: 30187663; PubMed Central PMCID: PMC6125245
Barnes EA, Lee L, Barnes SL, Brenner R, Alvira CM, Cornfield DN. β1-Subunit of the calcium-sensitive potassium channel modulates the pulmonary vascular smooth muscle cell response to hypoxia. Am J Physiol Lung Cell Mol Physiol. 2018 Aug 1;315(2):L265-L275. doi: 10.1152/ajplung.00060.2018. Epub 2018 Apr 12. PubMed PMID: 29644895.
Jaffe DB, Brenner R. A computational model for how the fast after hyperpolarization paradoxically increases gain in regularly firing neurons. J Neurophysiol. 2018 Apr 1;119(4):1506-1520. doi: 10.1152/jn.00385.2017. Epub 2018 Jan 10. PubMed PMID: 29357445.
Hu Z, Riquelme MA, Wang B, Bugay V, Brenner R, Gu S, Jiang JX. Cataract-associated connexin 46 mutation alters its interaction with calmodulin and function of hemichannels. J Biol Chem. 2018 Feb 16;293(7):2573-2585. doi: 10.1074/jbc.RA117.001348. Epub 2018 Jan 3. PubMed PMID: 29298900; PubMed Central PMCID: PMC5818178.
Whitmire LE, Ling L, Bugay V, Carver CM, Timilsina S, Chuang HH, Jaffe DB, Shapiro MS, Cavazos JE, Brenner R. Downregulation of KCNMB4 expression and changes in BK channel subtype in hippocampal granule neurons following seizure activity. PLoS One. 2017 Nov 16;12(11):e0188064. doi: 10.1371/journal.pone.0188064. eCollection 2017. PubMed PMID: 29145442; PubMed Central PMCID: PMC5690595.
Wang B, Bugay V, Ling L, Chuang HH, Jaffe DB, Brenner R. Knockout of the BK β4-subunit promotes a functional coupling of BK channels and ryanodine receptors that mediate a fAHP-induced increase in excitability. J Neurophysiol. 2016 Aug 1;116(2):456-65. doi: 10.1152/jn.00857.2015. Epub 2016 May 4. PubMed PMID: 27146987; PubMed Central PMCID: PMC4978790.
Zhang D, Wang X, Wang B, Garza JC, Fang X, Wang J, Scherer PE, Brenner R, Zhang W, Lu XY. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Mol Psychiatry. 2017 Jul;22(7):1044-1055. doi: 10.1038/mp.2016.58. Epub 2016 May 3. PubMed PMID: 27137743; PubMed Central PMCID: PMC5491689.
Wang B, Jaffe DB, Brenner R. Current understanding of iberiotoxin-resistant BK channels in the nervous system. Front Physiol. 2014 Oct 9;5:382. doi:10.3389/fphys.2014.00382. eCollection 2014. Review. PubMed PMID: 25346692; PubMed Central PMCID: PMC4190997.
Brenner R. Knockout of the BK β2 subunit reveals the importance of accessorizing your channel. J Gen Physiol. 2014 Nov;144(5):351-6. doi: 10.1085/jgp.201411291. Epub 2014 Oct 13. PubMed PMID: 25311634; PubMed Central PMCID: PMC4210423.
Evseev AI, Semenov I, Archer CR, Medina JL, Dube PH, Shapiro MS, Brenner R. Functional effects of KCNQ K(+) channels in airway smooth muscle. Front Physiol. 2013 Oct 7;4:277. doi: 10.3389/fphys.2013.00277. eCollection 2013. PubMed PMID: 24109455; PubMed Central PMCID: PMC3791379.
Brenner R, Wilcox KS. Potassium Channelopathies of Epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper’s Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK98143/ PubMed PMID: 22787671.
Semenov I, Herlihy JT, Brenner R. In vitro measurements of tracheal constriction using mice. J Vis Exp. 2012 Jun 25;(64). pii: 3703. doi: 10.3791/3703. PubMed PMID: 22760068; PubMed Central PMCID: PMC3476384.
Petrik D, Wang B, Brenner R. Modulation by the BK accessory β4 subunit of phosphorylation-dependent changes in excitability of dentate gyrus granule neurons. Eur J Neurosci. 2011 Sep;34(5):695-704. doi: 10.1111/j.1460-9568.2011.07799.x. Epub 2011 Aug 16. PubMed PMID: 21848922; PubMed Central PMCID: PMC3168689.
Jaffe DB, Wang B, Brenner R. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels. Neuroscience. 2011 Sep 29;192:205-18. doi: 10.1016/j.neuroscience.2011.06.028. Epub 2011 Jul 1. PubMed PMID: 21723921; PubMed Central PMCID: PMC3166373.
Semenov I, Wang B, Herlihy JT, Brenner R. BK channel β1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization. J Physiol. 2011 Apr 1;589(Pt 7):1803-17. doi: 10.1113/jphysiol.2010.204347. Epub 2011 Feb 7. PubMed PMID: 21300746; PubMed Central PMCID: PMC3099031
Shruti S, Urban-Ciecko J, Fitzpatrick JA, Brenner R, Bruchez MP, Barth AL.The brain-specific Beta4 subunit downregulates BK channel cell surface expression. PLoS One. 2012;7(3):e33429. doi: 10.1371/journal.pone.0033429. Epub 2012 Mar 16. Erratum in: PLoS One. 2012 May;7(5): doi/10.1371/annotation/64524ba8-f739-4fa8-93bf-862b160dca5c. PubMed PMID: 22438928; PubMed Central PMCID: PMC3306404.