The Journal of General Physiology
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online March 17, 2008
doi:10.1085/jgp.200709907
The Journal of General Physiology, Vol. 131, No. 4, 325-334
The Rockefeller University Press, 0022-1295 $30.00
© 2008 Qin et al.
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JGP
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qin, J.
Right arrow Articles by Fill, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qin, J.
Right arrow Articles by Fill, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Luminal Ca2+ Regulation of Single Cardiac Ryanodine Receptors: Insights Provided by Calsequestrin and its Mutants



Jia Qin1, Giorgia Valle2, Alma Nani1, Alessandra Nori2, Nicoletta Rizzi3, Silvia G. Priori3, Pompeo Volpe2, and Michael Fill1

1 Department of Molecular Physiology and Biophysics, Rush University Medical Center, Chicago, IL 60612
2 Department of Experimental Biomedical Sciences, University of Padova, Padova 35128, Italy
3 Department of Cardiology, University of Pavia IRCCS Fondazione Maugeri, Pavia 27100, Italy

Correspondence to Michael Fill: mfill{at}rush.edu

The luminal Ca2+ regulation of cardiac ryanodine receptor (RyR2) was explored at the single channel level. The luminal Ca2+ and Mg2+ sensitivity of single CSQ2-stripped and CSQ2-associated RyR2 channels was defined. Action of wild-type CSQ2 and of two mutant CSQ2s (R33Q and L167H) was also compared. Two luminal Ca2+ regulatory mechanism(s) were identified. One is a RyR2-resident mechanism that is CSQ2 independent and does not distinguish between luminal Ca2+ and Mg2+. This mechanism modulates the maximal efficacy of cytosolic Ca2+ activation. The second luminal Ca2+ regulatory mechanism is CSQ2 dependent and distinguishes between luminal Ca2+ and Mg2+. It does not depend on CSQ2 oligomerization or CSQ2 monomer Ca2+ binding affinity. The key Ca2+-sensitive step in this mechanism may be the Ca2+-dependent CSQ2 interaction with triadin. The CSQ2-dependent mechanism alters the cytosolic Ca2+ sensitivity of the channel. The R33Q CSQ2 mutant can participate in luminal RyR2 Ca2+ regulation but less effectively than wild-type (WT) CSQ2. CSQ2-L167H does not participate in luminal RyR2 Ca2+ regulation. The disparate actions of these two catecholaminergic polymorphic ventricular tachycardia (CPVT)–linked mutants implies that either alteration or elimination of CSQ2-dependent luminal RyR2 regulation can generate the CPVT phenotype. We propose that the RyR2-resident, CSQ2-independent luminal Ca2+ mechanism may assure that all channels respond robustly to large (>5 µM) local cytosolic Ca2+ stimuli, whereas the CSQ2-dependent mechanism may help close RyR2 channels after luminal Ca2+ falls below ~0.5 mM.

Abbreviations used in this paper: BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; CICR, Ca2+-induced Ca2+ release; CPVT, catecholaminergic polymorphic ventricular tachycardia; RyR2, type-2 ryanodine receptor; WT, wild-type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Physiol.Home page
L. Royer, S. Pouvreau, and E. Rios
Evolution and modulation of intracellular calcium release during long-lasting, depleting depolarization in mouse muscle
J. Physiol., October 1, 2008; 586(19): 4609 - 4629.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
N. Rizzi, N. Liu, C. Napolitano, A. Nori, F. Turcato, B. Colombi, S. Bicciato, D. Arcelli, A. Spedito, M. Scelsi, et al.
Unexpected Structural and Functional Consequences of the R33Q Homozygous Mutation in Cardiac Calsequestrin: A Complex Arrhythmogenic Cascade in a Knock In Mouse Model
Circ. Res., August 1, 2008; 103(3): 298 - 306.
[Abstract] [Full Text] [PDF]


  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents