Caffeine-induced [Ca2+] oscillations in neurones of frog sympathetic ganglia

1. Single cell fluorimetry was used to monitor caffeine-induced oscillations of cytosolic [Ca2+] in frog sympathetic ganglion neurones in 2.0 mM K+ Ringer solution. 2. [Ca2+] oscillations decreased in frequency and exhibited three different amplitude patterns after the first large peak of [Ca2+]: (a) a series of big oscillations (BOs) of constant large amplitude (300-400 nM), (b) a series of much smaller oscillations (SOs) (40-80 nM), or (c) a series of decaying oscillations (DOs) of rapidly decreasing amplitude. 3. A model in which the oscillation amplitude was determined by the Ca2+ content of the endoplasmic reticulum (ER) whereas the oscillation frequency was controlled by how rapidly the cytosolic [Ca2+] reached the threshold for Ca2+-induced Ca2+ release (CICR) was able to simulate each observed pattern by varying the level of activity of the ER Ca2+ pump (SERCA), CICR and release-activated Ca2+ transport (RACT). A cumulative, cytosolic Ca2+-dependent inactivation of the plasma membrane (PM) Ca2+ influx or of the Ca2+-sensitive leak coefficient of the ryanodine receptors caused the oscillation frequency to decrease in the model. 4. Transitions between BOs and SOs and changes in [Ca2+] oscillations caused by ryanodine, thapsigargin, lanthanum and FCCP could also be simulated. 5. We conclude that RACT, SERCA, CICR and Ca2+-dependent PM Ca2+ influx are major mechanisms underlying [Ca2+] oscillations in these neurones.