Inhibition of sarcoplasmic reticulum function by polyunsaturated fatty acids in intact, isolated myocytes from rat ventricular muscle

Abstract

We have studied the effects of two polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on spontaneous and electrically stimulated contractions in single, isolated ventricular myocytes from rat hearts. The frequency of spontaneous waves of calcium release and contraction (induced by elevation of the bathing calcium concentration) is reduced in the presence of EPA. At the same time the resting level of intracellular calcium falls, the resting cell length increases and the amplitude of shortening decreases. All these effects are reversed on removal of EPA. Imaging of the waves of calcium release shows that the amplitude and the rate of propagation of the wave is increased in EPA. Consistent with the increased amplitude, integration of the caffeine‐induced Na+‐Ca2+ exchange current (a measure of the sarcoplasmic reticulum (SR) calcium content) is increased by both EPA and DHA. EPA has a maintained negative inotropic effect on voltage clamped myocytes. This seems to be entirely due to inhibition of the L‐type calcium current. Smaller depolarising pulses in control conditions that elicit the same calcium current as in EPA also activate the same level of contraction. This is in spite of the increased SR calcium content in EPA. It is concluded that PUFAs have two effects on the SR; they reduce the availability of calcium for uptake and they inhibit the release mechanism. Both of these effects should lower the frequency of spontaneous waves of calcium release. As spontaneous release of calcium can initiate arrhythmias, some of the anti‐arrhythmic action of PUFAs must be exerted at the level of the SR.

CD36 Protein Influences Myocardial Ca2+ Homeostasis and Phospholipid Metabolism

“…Previously, calcium-independent phospholipase A 2 ␥ overexpression in the heart resulted in fasting-induced hemodynamic dysfunction (62). Changes in FA composition of phospholipids modulate functioning of membrane proteins (63), intracellular signal transduction, and gene transcription (64,65). There is evidence to support the importance of shifts toward lower n3/n6 FA content in phospholipids during myocardial adaptation to energy shortage such as with hibernation (66), which may serve to boost SR Ca 2ϩ uptake and Ca 2ϩ transients (67,68).…”

Effects of oleic acid on the high threshold barium current in seabassDicentrarchus labraxventricular myocytes

“…(Xiao et al, 1997;Pepe et al, 1994;Hallaq et al, 1992;Ferrier et al, 2002). The same n-3 PUFA can decrease cardiac sarcoplasmic reticulum Ca 2+ release (Negretti et al, 2000;Swan et al, 2003;Honen et al, 2003). Those effects of n-3 PUFA are known to protect hearts against arrhythmia induced by Ca 2+ overload.…”

Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research

“…79 Intracellular Ca 2ϩ "waves" represent propagated release of SR Ca 2ϩ and are an underlying focal mechanism for arrhythmia initiation. Shortterm 126,131,132,140 and long-term (dietary) 79 n-3 fatty acid supplementation both suppress the frequency of Ca 2ϩ waves and can reduce dyssynchronous beating in response to isoproterenol. The apparent difference in the effects of shortterm and long-term n-3 fatty acid supplementation on SR Ca 2ϩ suggests that different cellular mechanisms may be responsible for Ca 2ϩ wave suppression by short-term and long-term (dietary) n-3 fatty acid supplementation.…”

“…For example, isolated rat ventricular myocytes show a transient increase in contraction followed by a more sustained decrease, whereas guinea pig ventricular myocytes exhibit a monotonic decrease in contraction amplitude after short-term application of EPA. 129 Short-term application of n-3 fatty acids causes an increase in SR Ca 2ϩ content 126 and a reduction in ryanodine receptor openings. 138,139 In contrast, dietary n-3 fatty acid supplementation may not increase SR Ca 2ϩ content.…”