Cellular calcium fluctuations in mammalian heart: Direct evidence from noise analysis of aequorin signals in Purkinje fibers

Indirect evidence suggests that fluctuations, or oscillations, in the intracellular free calcium concentrations ([Ca²⁺](i)) can occur spontaneously in intact cardiac preparations, but such [Ca²⁺](i) fluctuations have never been demonstrated directly. We used the bioluminescent Ca²⁺-sensitive protein aequorin to detect fluctuations in the [Ca²⁺](i) in canine cardiac Purkinje fibers. Noise analysis of the aequorin luminescence reveals prominent peaks of power density at frequencies of 1-4 Hz; these peaks become larger and shift to higher frequencies as the [Ca²⁺](i) increases. Caffeine and ryanodine abolish the [Ca²⁺](i) fluctuations, suggesting that Ca²⁺ release and uptake by the sarcoplasmic reticulum generate these events. When [Ca²⁺](i) fluctuations are present, less tension is produced at any given level of mean aequorin luminescence. Thus, [Ca²⁺](i) fluctuations will undermine attempts to relate [Ca²⁺](i) and force in intact myocardium.