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) (40-60 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.
Cseresnyés
Z
Z
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene Street, Baltimore, MD 21201,, USA.
Bustamante
A I
AI
Schneider
M F
MF
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D007811:Lanthanum / Q000494:pharmacology; D008959:Models, Neurological; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D010507:Periodicity; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D012433:Ryanodine / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009840:Oligomycins; D010726:Phosphodiesterase Inhibitors; D014475:Uncoupling Agents; D012433:Ryanodine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002110:Caffeine; D019284:Thapsigargin; D007811:Lanthanum; D011188:Potassium; D002118:Calcium