Maura Porta, Ph.D.

Assistant Professor


Midwestern University
CCOM
Department of Physiology
Science Hall 422-C
555 31st St.
Downers Grove, IL 60515

Office: (630) 515-6962
e-mail: mporta@midwestern.edu

EDUCATION

MS Pharmaceutical Chemistry and Technologies  University of Genova (Italy) 2000
Ph.D. Physiology    
Loyola University Chicago 2006

RESEARCH SUMMARY

Currently the lab focuses on the study of ryanodine receptors calcium release channels and other sarcoplasmic reticulum channels reconstituted in planar lipid bilayers.

At the basis of striated muscle contraction there is a phenomenon called excitation-contraction coupling (ECC). A depolarizing stimulus across the plasma membrane of myocytes and muscle fibers induces opening of voltage gated calcium channels (L-type calcium channels, also known as dihydropyridine receptors, DHPR). The ensuing inward calcium current in cardiac myocytes activates ryanodine receptors calcium release channels (RyRs), which allow diffusion of calcium from the sarcoplasmic reticulum (SR) to the cytosol. The combination of calcium entry from the extracellular fluid and from the SR makes it possible for the intracellular calcium levels to rise markedly in a very restricted time frame. This calcium-induced calcium release is quickly terminated, but a definitive mechanism for this event has not yet been fully elucidated. A possible explanation for this behavior can be evinced by investigating an interesting aspect or RyR activity: their ability to work in teams.

RyR's are grouped in geometrically organized arrays on the SR membrane and in order to generate a uniform and fast rise in intracellular calcium;they must operate synchronously. We call this phenomenon coupled (or coordinated) gating. It is possible to study this property in artificial planar lipid bilayers, because this complex architecture can be partially retained, under certain circumstances, once the SR is broken apart into the microsomes we use for our reconstitutions.

PROJECT 1: We aim to determine whether RyR's require other proteins to achieve their coordination or if a direct channel-channel interaction is sufficient. Comparison of RyR's from adult and neonatal hearts could help to clarify this issue. In neonatal myocytes, RyR's play a relatively marginal role, since most of the calcium ions for contraction come from the extracellular fluid via voltage-gated calcium channels. In fact, neonatal arrays of RyR's are immature. Thus, here the hypothesis is that neonatal RyR's might lack some element crucial for coordination; therefore their ability to become coupled is reduced. These bilayer studies will be supported by confocal images of the distribution of RyR's and their ancillary proteins in adult and neonatal cardiomyocytes.

PROJECT 2: An ongoing collaboration with Dr. Mejia-Alvarez explores another aspect of the modulation of calcium release: the role of the chloride and potassium channels of the SR. As positive charges leave the SR during RyR activation, a voltage potential should build up across the SR membrane. This potential would rapidly impede further release of calcium. However, in the adult heart, calcium release is relatively long. We hypothesize that this is possible because of counteracting currents of:

We ask whether these mechanisms are already in place in the neonatal SR. The absence of such mechanisms would explain at least partially the shorter duration of the SR calcium release in neonatal hearts. To study this problem we are using both bilayers and confocal microscopy techniques.

Selected Publications

  1. Eudistomin D and penaresin derivatives as modulators of ryanodine receptor channels and sarcoplasmic reticulum Ca2+ ATPase in striated muscle. Diaz-Sylvester PL, Porta M, Juettner VV, Lv Y, Fleischer S, Copello JA. Mol Pharmacol. 2014 Apr;85(4):564-75. doi: 10.1124/mol.113.089342. Epub 2014 Jan 14.
  2. Coupled gating of skeletal muscle ryanodine receptors is modulated by Ca2+, Mg2+, and ATP. Porta M, Diaz-Sylvester PL, Neumann JT, Escobar AL, Fleischer S, Copello JA. Am J Physiol Cell Physiol. 2012 Sep 15;303(6):C682-97. doi: 10.1152/ajpcell.00150.2012. Epub 2012 Jul 11.
  3. Modulation of cardiac ryanodine receptor channels by alkaline earth cations. Diaz-Sylvester PL, Porta M, Copello JA. PLoS One. 2011;6(10):e26693. doi: 10.1371/journal.pone.0026693. Epub 2011 Oct 21.
  4. Single ryanodine receptor channel basis of caffeine's action on Ca2+ sparks. Porta M, Zima AV, Nani A, Diaz-Sylvester PL, Copello JA, Ramos-Franco J, Blatter LA, Fill M. Biophys J. 2011 Feb 16;100(4):931-8. doi: 10.1016/j.bpj.2011.01.017.
  5. Flux regulation of cardiac ryanodine receptor channels. Liu Y, Porta M, Qin J, Ramos J, Nani A, Shannon TR, Fill M. J Gen Physiol. 2010 Jan;135(1):15-27. doi: 10.1085/jgp.200910273. Epub 2009 Dec 14.
  6.  Trifluoperazine: a rynodine receptor agonist. Qin J, Zima AV, Porta M, Blatter LA, Fill M. Pflugers Arch. 2009 Aug;458(4):643-51. doi: 10.1007/s00424-009-0658-y. Epub 2009 Mar 11.
  7.  Ryanoids and imperatoxin affect the modulation of cardiac ryanodine receptors by dihydropyridinereceptor Peptide A. Porta M, Diaz-Sylvester PL, Nani A, Ramos-Franco J, Copello JA. Biochim Biophys Acta. 2008 Nov;1778(11):2469-79. doi: 10.1016/j.bbamem.2008.07.024. Epub 2008 Aug 3.
  8. Halothane modulation of skeletal muscle ryanodine receptors: dependence on Ca2+, Mg2+, and ATP. Diaz-Sylvester PL, Porta M, Copello JA. Am J Physiol Cell Physiol. 2008 Apr;294(4):C1103-12. doi: 10.1152/ajpcell.90642.2007. Epub 2008 Feb 27.
  9.  Differential activation by Ca2+, ATP and caffeine of cardiac and skeletal muscle ryanodinereceptors after block by Mg2+. Copello JA, Barg S, Sonnleitner A, Porta M, Diaz-Sylvester P, Fill M, Schindler H, Fleischer S. J Membr Biol. 2002 May 1;187(1):51-64.