Universidad Nacional Autonoma de Mexico | 1982 | M.D.
My research focuses on understanding the mechanisms of Ca2+ release from intracellular stores (i.e. sarco/endoplasmic reticulum; SR, ER) in excitable cells. Specifically, I am interested on defining the mechanisms by which the Ca2+ release units, formed by either ryanodine receptors (RyRs) or inositol-trisphosphate receptors (IP3R), operate in conjunction with the Ca2+ channels (DHPRs) located in the cell membrane. To this end, the functional attributes of Ca2+ release events are studied at the global (cellular Ca2+ transient), local (Ca2+ sparks, puffs, and waves), and molecular (single-channel activity) levels and interpreted in the context of cellular signal transduction processes, like excitation-contraction coupling (ECC) and IP3-activated pathways.
These studies are conducted using a multidisciplinary experimental approach that combines immunocytochemistry, molecular/cellular electrophysiology, and fluorescence microscopy (linescan confocal imaging of Ca2+ signals in single cells and pulsed local-field in whole, beating hearts). My long term goal is that, by defining the molecular mechanism(s) of Ca2+ signaling in excitable cells, new insights about local Ca2+ control of Ca2+ release channels will arise.
Downers Grove, IL
Chicago College of Optometry
Chicago College of Osteopathic Medicine
College of Dental Medicine-Illinois
College of Graduate Studies - IL
College of Health Sciences - IL
Biomedical Sciences (M.A.)
Biomedical Sciences (M.B.S.)
Physician Assistant Studies
Universidad Nacional Autonoma de Mexico | 1982 | M.D.
“Neuron & Muscle Physiology” in “Human Physiology 1510”.
“Obesity & Cardiovascular Disease” & "Skeletal Muscle Disorders" in “Pathophysiology 0580”.
“Autonomic Nervous System, Muscle, & Circulatory Physiology”, in “Human Physiology 1501”.
“Endocrine System Physiology”, in “Human Physiology 1502”.
“Neuron & Muscle Physiology” & “Diseases of Peripheral Nerves” in IBSSD 1521 “Clinical Neurosciences”.
“Circulatory Physiology” & “Cardiac Pathophysiology” in IBSSD1531 “Cardiovascular System”.
- “IP3R-mediated Ca2+ signals from the endoplasmic reticulum”. This project's goal is to define the fundamental mechanisms that control the function of IP3-sensitive intracellular Ca2+ release channels, known as receptors (IP3R). The hypothesis tested here is that the existence of a single residue (D2594) in the channel’s permeation pore determines the luminal Ca2+ dependency exhibited by IP3R and that mutations of this residue substantially affect the biophysical properties of the resulting Ca2+ release events. Therefore, our goal is to determine the molecular mechanisms by which the D2594 mutation affect IP3R1 activity and Ca2+ dynamics when the D2594 residue is replaced by a basic residue (i.e. lysine). To this end, the biophysical properties (i.e. amplitude, frequency, & kinetics) of local Ca2+ release events (Ca2+ puffs) are defined, compared and contrasted between HEK cells expressing either the wild type or the D2594K mutant IP3R. This project is based on real-time confocal imaging of intracellular Ca2+ signals.
- “Impact of Ca2+ release from the sarcoplasmic reticulum (SRCa) on the action potential (AP) morphology in mouse heart”. The goal of this project is studying in intact beating whole hearts, the cardio-protective effects of a peptide present in a scorpion venom called imperalcin (ImpCa), that supposedly prevents/rescues events of cathecolaminergic polymorphic ventricular tachycardia (CPVT). It has recently been found that in a CPVT-prone transgenic mouse expressing a loss-of-function mutated form of the ryanodine receptor (RyR2-A4860G+/-), ImpCa specifically binds to the RyR to terminate CPVT events. The hypothesis tested in this project is that ImpCa increases the Ca2+ leak through RyR channels, preventing/reverting the Ca2+ SR overload that presumably over-activates the Na+-Ca2+ exchanger (NCX), and thereby decreasing the appearance of afterdepolarizations that typically trigger the appearance of CPVT episodes. For this project, intracellular Ca2+ transients are measured as fluorescence signals in intact-beating whole hearts with a technique called pulsed local-field fluorescence microscopy (PLFFM), while the action potentials are simultaneously recorded with the microelectrodes technique.
Aguilar-Sánchez, Y., D. Fainstein, R. Mejía-Alvarez, A. L. Escobar (2017). Local Field Fluorescence Microscopy: Imaging cellular signals in intact hearts. Journal of Visualized Experiments. (121). doi: 10.3791/55202.
Escobar, A.L., C.G. Pérez, M.E. Reyes, S.G. Lucero, D. Kornyeyev, R. Mejía-Alvarez, & J. Ramos-Franco. (2012). Role of inositol-1,4,5-trisphosphate in the regulation of ventricular Ca2+ signaling in intact mouse heart. Journal of Molecular and Cellular Cardiology. 53(6):768-779.
Snopko, RM., J. Ramos-Franco, A. Di Maio, K.L. Karko, C. Manley, E. Piedras-Rentería, & R. Mejía-Alvarez. (2008). Ca2+ sparks and cellular distribution of ryanodine receptors in developing cardiomyocytes from rat. Journal of Molecular and Cellular Cardiology. 44(6):1032-1044.
Di Maio, A., K.L. Karko, R.M. Snopko, R. Mejía-Alvarez, & C. Franzini-Armstrong. (2007). T-tubule formation in cardiomyocytes: two possible mechanisms? Journal of Muscle Research and Cell Motility. 28(4-5):231-41.
Escobar, A.L., R. Ribeiro-Costa, C. Villalba-Galea, M.E. Zoghbi, C.G. Pérez, & R. Mejía-Alvarez. (2004). Developmental changes of intracellular Ca2+ transients in beating rat hearts. American Journal of Physiology. 286: H971-H978.
Latin-American Biophysical Society (SOBLA).
American Physiological Society.
2015-2019 NIH. Co-Investigator (in consortium with Rush University Medical Center). Research grant R01 GM111397-01A1. Project Title: “Control of IP3R-mediated Ca2+ Release”.