FLUCTUATIONS IN THE INTENSITY OF LIGHT SCATTERED THROUGH DIASTOLIC CARDIAC MUSCLE

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We have discovered that scattered light intensity fluctuations (SLIF) are present in isolated rat ventricular muscle even under conditions formerly considered to be quiescent. Subsequent experiments indicate that SLIF are highly dependent on Ca2+ loading of the cell and could be reversibly terminated (1) by maintaining constant Ca2+ concentration in the myofilament space in skinned fibers or (2) in intact fibers by caffeine. These results were interpreted to indicate that cellular myoplasmic Ca2+ concentration oscillates in diastole, producing motion of the myofilaments, which modulates the laser beam and results in SLIF. This myofilament motion which is asynchronous within a cell, and among cells, results in a small degree of diastolic force or "tone" in the muscle. Additional experiments have demonstrated SLIF in atrial, ventricular, and conduction tissues in a range of mammalian species including man and indicate the universality of this phenomenon in excitable cardiac tissues. In collaboration with the Department of Physiology at the University of Maryland, we have directly demonstrated these Ca2+ oscillations utilizing intracellular injects of the chemiluminescent protein, aequorin. In our most recent studies we have time gated SLIF measurements following stimulation in order to determine the restitution of action potential stimulated Ca2+ release relative to the restitution of SLIF following a previous action potential mediated release. We found that stimulation increases SLIF frequency in this diastolic window and that antiarrhythmic aspects suppress this increase. In our most recent studies we have also demonstrated the presence of SLIF in the intact perfused heart and have shown that it covaries with Ca2+-dependent tone.