Gradual caffeine-induced Ca2+ release in mouse dorsal root ganglion neurons is controlled by cytoplasmic and luminal Ca2+.
Cytosolic free calcium concentration ([Ca2+]c) was recorded from acutely isolated mouse dorsal root ganglion neurons loaded with Ca(2+)-indicator indo-1. The initiation of intracellular Ca2+ release by low (1-5 mM) caffeine concentrations failed to completely empty the caffeine-sensitive stores; subsequent challenge with higher doses of caffeine produced an additional [Ca2+]c elevation. This indicates a gradual Ca2+ release from caffeine-sensitive stores. The sensitivity of Ca2+ stores to caffeine was strongly influenced by endoplasmic reticulum luminal Ca2+ concentration ([Ca2+]i) as an increase in [Ca2+]i produced by a conditioning depolarization-induced Ca2+ entry, caused a several fold decrease of caffeine EC50. By elevating [Ca2+]c a threshold concentration (about 350 nM) can be reached, at which low doses of caffeine (2-5 mM) produced a regenerative Ca2+ release, that depletes the Ca2+ stores almost completely, indicating that all-or-nothing Ca(2+)-induced Ca2+ release can be generated in nerve cells.
Shmigol
A
A
International Center of Molecular Physiology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Svichar
N
N
Kostyuk
P
P
Verkhratsky
A
A
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000378:metabolism*; D009994:Osmolar Concentration
D002110:Caffeine; D002118:Calcium