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 concentration [( 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.