Edward Perez-Reyes

Education

  • BA, University of North Carolina
  • PhD, University of Colorado, Denver
  • Postdoc, Stanford University

Primary Appointment

  • Professor, Pharmacology

Contact

Research Interest(s)

Molecular pharmacology of voltage-gated calcium channels

Research Description

Calcium entry via voltage-gated Ca2+ channels is a key event in neuronal firing, muscle contraction, gene expression, and secretion of neurotransmitters and hormones. Voltage-gated Ca2+ channels are the site of action of a number of clinically relevant drugs, termed "calcium channel blockers." Typically these drugs are used to treat hypertension and angina, but recent evidence suggests that similar blockers might be useful for epilepsy and pain.

The Perez-Reyes laboratory is focused on determining the molecular structure of voltage-gated calcium channels, then studying how their structure relates to the function and pharmacology of the channel (review).

Early studies focused on the cloning and expression of the skeletal and cardiac muscle L-type channels. These studies established that the alpha1 subunit contains both the ion permeation pathway and is the receptor for most calcium channel blockers. These studies also elucidated the important role that auxiliary subunits play in the formation of active channels and drug receptors. A key contribution was the cloning of low voltage-activated T-type Ca2+ channels, which has opened the door to studies on their biophysics, localization, role in neuronal excitability, and pharmacology. This work combined a number of exciting techniques such as bioinformatics, molecular cloning, and electrophysiological recordings of whole cell and single channel currents. We believe that up regulation of T-type channels may underlie many pathological states including thalamocortical dysrhythmias and epilepsy. To test this hypothesis we have examined their expression in animal models of epilepsy and studied how anti-epileptic drugs block the recombinant channels. Future work will be directed at regulating T-type channel levels in the brain, and studying the functional consequences of knocking out gene expression in transgenic mice. The laboratory is currently funded by grants from NIH.

Selected Publications

  • Dey D, Eckle V, Vitko I, Sullivan K, Lasiecka Z, Winckler B, Stornetta R, Williamson J, Kapur J, Perez-Reyes E. A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus. Epilepsia. 2013;55(2): 203-13. PMID: 24299204 | PMCID: PMC4161023
  • Eckle V, Shcheglovitov A, Vitko I, Dey D, Yap C, Winckler B, Perez-Reyes E. Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility. The Journal of physiology. 2013;592 795-809. PMID: 24277868 | PMCID: PMC3934715
  • Shcheglovitov A, Vitko I, Lazarenko R, Orestes P, Todorovic S, Perez-Reyes E. Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Ca(v)2.3 calcium channels. The Journal of general physiology. 2012;139(3): 219-34. PMID: 22371363 | PMCID: PMC3289959
  • Hargus N, Jennings C, Perez-Reyes E, Bertram E, Patel M. Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A(1)-receptor activation. Epilepsia. 2011;53(1): 168-76. PMID: 22126400 | PMCID: PMC3253213
  • Characterization of the gating brake in the I-II loop of CaV3 T-type calcium channels. Channels (Austin, Tex.). 2010;4(6): 453-8. PMID: 21099341 | PMCID: PMC3052245
  • Arias-Olguín I, Vitko I, Fortuna M, Baumgart J, Sokolova S, Shumilin I, Van Deusen A, Soriano-García M, Gomora J, Perez-Reyes E. Characterization of the gating brake in the I-II loop of Ca(v)3.2 T-type Ca(2+) channels. The Journal of biological chemistry. 2008;283(13): 8136-44. PMID: 18218623 | PMCID: PMC2276388
  • Baumgart J, Vitko I, Bidaud I, Kondratskyi A, Lory P, Perez-Reyes E. I-II loop structural determinants in the gating and surface expression of low voltage-activated calcium channels. PloS one. 2008;3(8): e2976. PMID: 18714336 | PMCID: PMC2495038
  • Shcheglovitov A, Vitko I, Bidaud I, Baumgart J, Navarro-Gonzalez M, Grayson T, Lory P, Hill C, Perez-Reyes E. Alternative splicing within the I-II loop controls surface expression of T-type Ca(v)3.1 calcium channels. FEBS letters. 2008;582(27): 3765-70. PMID: 18930057 | PMCID: PMC2614674
  • Vitko I, Shcheglovitov A, Baumgart J, Arias-Olguín I, Murbartián J, Arias J, Perez-Reyes E. Orientation of the calcium channel beta relative to the alpha(1)2.2 subunit is critical for its regulation of channel activity. PloS one. 2008;3(10): e3560. PMID: 18958281 | PMCID: PMC2570331
  • Vitko I, Chen Y, Arias J, Shen Y, Wu X, Perez-Reyes E. Functional characterization and neuronal modeling of the effects of childhood absence epilepsy variants of CACNA1H, a T-type calcium channel. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2005;25(19): 4844-55. PMID: 15888660