How depolarization-induced Ca2+ entry or caffeine activates Ca2+-induced Ca
2+ release (CICR) in the cytoplasm and nucleoplasm was studied by recording
intracellular Ca2+ ([Ca2+](i)) with a confocal microscope in cultured bull
frog sympathetic ganglion cells. The amplitude and propagation speed of vol
tage pulse-induced rises in [Ca2+](i) were greater in the submembrane (< 5
mu m depth) region than in the core region, and delayed and smaller, but si
gnificant, in the nucleus. Ryanodine and dantrolene reduced the rises in [C
a2+](i) in both the cytoplasm and nucleus. A rapid applica tion of high Ksolution induced global rises in [Ca2+](i) in both the cytoplasm and nucleo
plasm, which were decreased by dantrolene. Caffeine produced a slow, small
rise in [Ca2+](i) which grew into a global, regenerative rise both in the c
ytoplasm and nucleoplasm with some inward gradient in the cytoplasm. Each o
f the high [Ca2+](i) phases during caffeine-induced [Ca2+](i) oscillation b
egan in the submembrane region, while low [Ca2+](i) phases started in the c
ore region. These results suggest that CICR activated by Ca2+ entry or caff
eine occurs predominantly in the submembrane region causing an inwardly spr
eading Ca2+ wave or [Ca2+](i) oscillations, and that the nuclear envelope c
an cause CICR in the nucleoplasm, which is delayed due to Ca2+ diffusion ba
rrier at the nuclear pores. (C) 2000 Harcourt Publishers Ltd.