APPS November 2002 Meeting Abstract 2413

Bonny N. Honen¹, Derek R. Laver², David A. Saint¹, 1. Department of Physiology, University of Adelaide, SA. 2. School of Biomedical Sciences, University of Newcastle, NSW.

Previous studies in out laboratory have shown that the dietary supplementation of rats with fish oil reduces the size of calcium sparks in atrial myocytes¹ and ventricular myocytes. We have also found that the acute addition of eicosapentaenoic acid (EPA, a fatty acid present in fish oil) to rat ventricular myocytes significantly reduces calcium spark size. A possible mechanism by which polyunsaturated fatty acids may reduce calcium spark size is by altering the gating of the sarcoplasmic reticulum calcium release channel, the ryanodine receptor (RyR).

The aim of this study was to determine the effects of EPA on the cardiac RyR and its sensitivity to cytosolic calcium. SR vesicles containing RyR were fused into artificial bilayers and were exposed to concentrations of EPA ranging between 10 and 50然 added to the cytosolic face or 50 然 EPA added to the luminal face of the channel. To determine the effects of EPA on RyR calcium sensitivity, calcium concentrations ranging between 0.1 然 and 0.1 mM were applied to the cytosolic face of the channel in the absence and presence of 50 然 EPA. The open probability of the RyR was reduced by 85% on the addition of 50 然 EPA to the cytosolic side of the channel. Similarly the RyR open probability decreased by 70% on the addition of 50 然 EPA to the luminal side of the channel. The calcium sensitivity of the RyR was not altered by EPA.

In conclusion, EPA exhibits a blocking effect on the cardiac ryanodine channel at concentrations similar to those that might be found in the cytosol during an ischemic event. As the effect of EPA is similar whether applied to the cytosolic or luminal side of the channel it is likely that EPA mediating its effect via the membrane.