S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes

Volkers, M. et al. (2007) S100A1 decreases calcium spark frequency and alters their spatial characteristics in permeabilized adult ventricular cardiomyocytes. Cell Calcium, 41(2), pp. 135-143. (doi:10.1016/j.ceca.2006.06.001) (PMID:16919727)

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Abstract

S100Al, a Ca2+-sensor protein of the EF-hand type, exerts positive inotropic effects in the heart via enhanced cardiac ryanodine receptor (RyR2) activity. Here we report that S100Al protein (0.1 mu M) interacts with the RyR2 in resting permeabilized cardiomyocytes at free Ca2+- levels comparable to diastolic Ca2+-concentrations (similar to 150 nM). Alterations of RyR2 function due to S100Al binding was assessed via analysis of Ca2+-spark characteristics. Ca2+-spark frequency, amplitude and duration were all reduced upon perfusion with 0. 1 mu M S100Al protein by 38%, 14% and 18%, respectively. Most likely, these effects were conveyed through the S100Al C-terminus (S100Al-ct; amino acids 75-94) as the corresponding S100Al-ct peptide (0.1 mu M) inhibited S100Al protein binding to the RyR2 andsimilarly attenuated frequency, amplitude and duration of Ca2+-sparks by 52%, 8% and 26%, respectively. Accordingly, the sarcoplasmic reticulum (SR) Ca2+-content was slightly increased but the stoichiometry of other accessory RyR2 modulators (sorcin/FKBP12.6) remained unaltered by S100Al. Hence, we propose S100Al as a novel inhibitory modulator of RyR2 function at diastolic Ca2+-concentrations in rabbit ventricular cardiomyocytes.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and MacQuaide, Dr Niall and Loughrey, Professor Christopher
Authors: Volkers, M., Loughrey, C.M., MacQuaide, N., Remppis, A., DeGeorge, B.R., Wegner, F.V., Friedrich, O., Fink, R.H.A., Koch, W.J., Smith, G.L., and Most, P.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Cell Calcium
Publisher:Elsevier
ISSN:0143-4160
ISSN (Online):1532-1991
Published Online:21 August 2006

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