Differential sensitivity of Ca2+ wave and Ca2+ spark events to ruthenium red in isolated permeabilised rabbit cardiomyocytes

MacQuaide, N. , Ramay, H.R., Sobie, E.A. and Smith, G.L. (2010) Differential sensitivity of Ca2+ wave and Ca2+ spark events to ruthenium red in isolated permeabilised rabbit cardiomyocytes. Journal of Physiology, 588(23), pp. 4731-4742. (doi: 10.1113/jphysiol.2010.193375)

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Spontaneous Ca2+ waves in cardiac muscle cells are thought to arise from the sequential firing of local Ca2+ sparks via a fire-diffuse-fire mechanism. This study compares the ability of the ryanodine receptor (RyR) blocker ruthenium red (RuR) to inhibit these two types of Ca2+ release in permeabilised rabbit ventricular cardiomyocytes. Perfusing with 600 nM Ca2+ (50 μM EGTA) caused regular spontaneous Ca2+ waves that were imaged with the fluorescence from Fluo-5F using a laser-scanning confocal microscope. Addition of 4 μM RuR caused complete inhibition of Ca2+ waves in 50% of cardiomyocytes by 2 minutes and in 100% by 4 minutes. Separate experiments used 350μM EGTA (600 nM Ca2+) to limit Ca2+ diffusion but allow the underlying Ca2+ sparks to be imaged. The time course of RuR-induced inhibition did not match that of waves. After 2 minutes of RuR, none of the characteristics of the Ca2+ sparks were altered, after 4 minutes Ca2+ spark frequency was reduced ~40%; no sparks could be detected after 10 minutes. Measurements of Ca2+ within the SR lumen using Fluo-5N showed an increase in intra-SR Ca2+ during the initial 2-4 minutes of perfusion with RuR in both wave and spark conditions. Computational modelling suggests that the sensitivity of Ca2+ waves to RuR block depends on the number of RyRs per cluster. Therefore inhibition of Ca2+-waves without affecting Ca2+-sparks may be explained by block of small, non-spark producing clusters of RyRs that are important to the process of Ca2+ wave propagation.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and MacQuaide, Dr Niall
Authors: MacQuaide, N., Ramay, H.R., Sobie, E.A., and Smith, G.L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Physiology
Published Online:04 October 2010

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