O'Neill, S.C., Miller, L. , Hinch, R. and Eisner, D.A. (2004) Interplay between SERCA and sarcolemmal Ca2+ efflux pathways controls spontaneous release of Ca2+ from the sarcoplasmic reticulum in rat ventricular myocytes. Journal of Physiology, 15(559), pp. 121-128. (doi: 10.1113/jphysiol.2003.058917) (PMID:15194743)
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Abstract
Waves of calcium‐induced calcium release occur in a variety of cell types and have been implicated in the origin of cardiac arrhythmias. We have investigated the effects of inhibiting the SR Ca2+‐ATPase (SERCA) with the reversible inhibitor 2′,5′‐di(tert‐butyl)‐1,4‐benzohydroquinone (TBQ) on the properties of these waves. Cardiac myocytes were voltage clamped at a constant potential between −65 and −40 mV and spontaneous waves evoked by increasing external Ca2+ concentration to 4 mm. Application of 100 μm TBQ decreased the frequency of waves. This was associated with increases of resting [Ca2+]i, the time constant of decay of [Ca2+]i and the integral of the accompanying Na+–Ca2+ exchange current. There was also a decrease in propagation velocity of the waves. There was an increase of the calculated Ca2+ efflux per wave. The SR Ca2+ content when a wave was about to propagate decreased to 91.7 ± 3.2%. The period between waves increased in direct proportion to the Ca2+ efflux per wave meaning that TBQ had no effect on the Ca2+ efflux per unit time. We conclude that (i) decreased wave frequency is not a direct consequence of decreased Ca2+ pumping by SERCA between waves but, rather, to more Ca2+ loss on each wave; (ii) inhibiting SERCA increases the chance of spontaneous Ca2+ release propagating at a given SR content.
Item Type: | Articles (Other) |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Miller, Dr Louise |
Authors: | O'Neill, S.C., Miller, L., Hinch, R., and Eisner, D.A. |
Subjects: | Q Science > QP Physiology |
College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
Journal Name: | Journal of Physiology |
Journal Abbr.: | J Physiol |
Publisher: | Wiley |
ISSN: | 0022-3751 |
ISSN (Online): | 1469-7793 |
Published Online: | 11 June 2004 |
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