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.
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.
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.
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.
Seibold MA, Wang B, Eng C, Kumar G, Beckman KB, Sen S, Choudhry S, Meade
K, Lenoir M, Watson HG, Thyne S, Williams LK, Kumar R, Weiss KB,
Grammer LC, Avila PC, Schleimer RP, Burchard EG, Brenner R. An african-specific functional polymorphism in KCNMB1 shows sex-specific association with asthma severity. Hum Mol Genet. 2008 Sep 1;17(17):2681-90.
Wang B, Rothberg BS, Brenner R. Mechanism of beta4 subunit modulation of BK channels. J Gen Physiol. 2006 Apr;127(4):449-65.