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

  • Vitko I, Bidaud I, Arias J, Mezghrani A, Lory P, Perez-Reyes E. The I-II loop controls plasma membrane expression and gating of Ca(v)3.2 T-type Ca2+ channels: a paradigm for childhood absence epilepsy mutations. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27(2): 322-30. PMID: 17215393
  • Xie X, Van Deusen A, Vitko I, Babu D, Davies L, Huynh N, Cheng H, Yang N, Barrett P, Perez-Reyes E. Validation of high throughput screening assays against three subtypes of Ca(v)3 T-type channels using molecular and pharmacologic approaches. Assay and drug development technologies. 2007;5(2): 191-203. PMID: 17477828
  • 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
  • Talley E, Sol√≥rzano G, Depaulis A, Perez-Reyes E, Bayliss D. Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat. Brain research. Molecular brain research. 2000;75(1): 159-65. PMID: 10648900