My research is focused on the control mechanisms of intracellular Ca2+ release in excitable cells. Specifically, my lab is interested on defining the biophysical properties of the inositol trisphosphate receptor (IP3R)- and ryanodine receptor (RyR)-mediated Ca2+ release from intracellular organelles. My ultimate goal is that, by defining the molecular mechanism(s) of Ca2+ signaling in excitable cells, a better understanding of their functional role can be gained under normal and pathological conditions.
Our work focuses on defining the channels’ structure-function relationships by studying the biophysical attributes of the intracellular Ca2+ release phenomenon.
To this end, the following projects are conducted:
- Study of the IP3R local Ca2+ control mechanisms using site-directed mutagenesis to identify key residues of the luminal Ca2+ sensing site in the IP3R molecule: This project’s goal is to understand the channel regulation by intra-organelle Ca2+ levels.
- Define the Ca2+ release process in the intact heart to understand the loss of Ca2+ regulation observed in pathologic states like ischemia-reperfusion.
- Define the biophysical properties of porins (e.g., Karlotoxins) in artificial planar bilayers: This project’s ultimate goal is to be able to understand the pathogenic mechanisms of these toxins in vivo.
We use a multidisciplinary approach to study IP3R and RyR mediated Ca2+ signaling from the single molecule to the whole organ levels. Such a multidisciplinary approach is based on the use of ion channel reconstitution into artificial planar lipid bilayers, biochemical and molecular biology techniques (i.e. recombinant protein expression), laser confocal microscopy and loose patch photolysis.
Ramos-Franco J, Fill M. "Approaching ryanodine receptor therapeutics from the calcin angle." J Gen Physiol. 2016 May;147(5):369-73. PMID: 27114611
Ramos-Franco J, Aguilar-Sanchez Y, Escobar AL. “Intact Heart Loose Patch Photolysis Reveals Ionic Current Kinetics During Ventricular Action Potentials.” Circ Res. 2016 Jan 22;118(2):203-15. PMID: 26565013
Escobar AL, Perez CG, Reyes ME, Lucero SG, Kornyeyev D, Mejía-Alvarez R, Ramos-Franco J. “Role of Inositol 1,4,5-Trisphosphate in the Regulation of Ventricular Ca2+ Signaling in Intact Mouse Heart.” J Mol Cell Cardiol. 2012 Dec; 53(6):768-79. PMID: 22960455
Porta M, Zima AV, Nani A, Diaz-Sylvester PL, Copello JA, Ramos-Franco J, Blatter LA, Fill M. “Single Ryanodine Receptor Channel Basis of Caffeine's Action on Ca2+ Sparks.” Biophys J. 2011 Feb 16; 100(4):931-8. PMID: 21320437
Ramos-Franco J, Gomez AM, Nani A, Liu Y, Copello JA, Fill M. “Ryanodol Action on Ca2+ Sparks in Ventricular Myocytes.” Pflugers Arch. 2010 Sep; 460(4):767-76. PMID: 20419313
Qin J, Valle G, Nani A, Chen H, Ramos-Franco J, Nori A, Volpe P, Fill M. "Ryanodine receptor luminal Ca2+ regulation: swapping calsequestrin and channel isoforms." Biophys J. 2009 Oct 7;97(7):1961-70. PMID: 19804727
Porta M, Diaz-Sylvester PL, Nani A, Ramos-Franco J, Copello JA. "Ryanoids and imperatoxin affect the modulation of cardiac ryanodine receptors by dihydropyridine receptor Peptide A." Biochim Biophys Acta. 2008 Nov;1778(11):2469-79. PMID: 18722342
Snopko RM, Ramos-Franco J, Di Maio A, Karko KL, Manley C, Piedras-Rentería E, Mejía-Alvarez R. "Ca2+ sparks and cellular distribution of ryanodine receptors in developing cardiomyocytes from rat." J Mol Cell Cardiol. 2008 Jun;44(6):1032-44. PMID: 18468619
Snopko RM, Aromolaran AS, Karko KL, Ramos-Franco J, Blatter LA, Mejía-Alvarez R. "Cell culture modifies Ca2+ signaling during excitation-contraction coupling in neonate cardiac myocytes." Cell Calcium. 2007 Jan;41(1):13-25. PMID: 16908061
Pérez CG, Copello JA, Li Y, Karko KL, Gómez L, Ramos-Franco J, Fill M, Escobar AL, Mejía-Alvarez R. "Ryanodine receptor function in newborn rat heart." Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2527-40. PMID: 15626694
Ramos J, Jung W, Ramos-Franco J, Mignery GA, Fill M. "Single channel function of inositol 1,4,5-trisphosphate receptor type-1 and -2 isoform domain-swap chimeras." J Gen Physiol. 2003 May;121(5):399-411. PMID: 12695486
Ramos-Franco J, Galvan D, Mignery GA, Fill M. “Location of the Permeation Pathway in the Recombinant Type 1 Inositol 1,4,5-Trisphosphate Receptor.” J Gen Physiol. 1999 Aug; 114(2):243-50. PMID: 10436000
Ramos-Franco J, Fill M, Mignery GA. “Isoform-Specific Function of Single Inositol 1,4,5-Trisphosphate Receptor Channels." Biophys J. 1998 Aug; 75(2):834-9. PMID: 9675184
Ongoing research support
- NIH R01-GM11397: “Control of IP3R-Mediated Ca2+ Release” (Principal investigator)
Completed research support
- NIH R01-HL57832: “Control Mechanisms of Ca2+ Induced Ca2+ Release” (Co-investigator)
- American Heart Association, Grant-in-Aid: “The Inositol Trisphosphate Receptor Quantal Ca2+ Release Mechanism” (Principal investigator)
- NIH R01-HL 071741: “Local Intracellular Ca2+ Release in Neonate Heart” (Principal investigator)
- Yuriana Aguilar, PhD, instructor
- Beatriz Martinez, MD, volunteer
- Nicolle Razimoff, research assistant
- Allison M Tambeaux, PhD candidate
Josefina Ramos-Franco MD, PhD
Rush University Medical Center
Department of Physiology & Biophysics
1298 Jelke South
1750 W. Harrison St.
Chicago, IL 60612