77open probability 8- to 16-fold and the mean open time of the channel 24- to 42-fold
(Thrower et al. 2003 ). This IP 3 R/Ca2+ channel-activating role is also shared with
CGA to a certain extent, but the magnitude of CGA effect on the Ca2+ channel is
markedly smaller than that exerted by CGB, consistent with the weaker interaction
strength of CGA for the IP 3 Rs. As a result, the IP 3 -dependent Ca2+ mobilization in
the cell is heavily affected by the subcellular localization of CGB inside the cell.
6 Concentration of CGB and the IP 3 Rs in Secretory
Granules, ER, and Nucleus
The CGB concentrations in secretory granules and the ER in the typical neuroendo-
crine adrenal chromaffin cells are ~200 μM and 120 μM, respectively (Huh et al.
2005a), while the relative IP 3 R concentrations in secretory granules and the ER are
~3.5 and ~1.0, respectively, when that of the nucleus is taken as 1.0 (Huh et al.
2005c). That secretory granules contain the highest concentrations of CGB and the
IP 3 Rs, and the largest amounts of CGB and the IP 3 Rs, than any other organelle in
the cytoplasm naturally points to the more prominent role of secretory granules in
IP 3 -dependent Ca2+ signaling, i.e., higher IP 3 sensitivity of the granule IP 3 R/Ca2+
channels than that of the ER and the markedly larger amounts of Ca2+ released from
secretory granules than from the ER (Huh et al. 2007 ).
Unlike the more easily identifiable molecular organization of secretory granules
and the ER, the situation in the nucleus is a bit more complicated. The CGB concen-
tration in the nucleus is estimated to be ~80 μM (Huh et al. 2005a), a figure that
shows average CGB concentration in the whole nucleus although CGB localization
is limited only to the small IP 3 -sensitive nucleoplasmic Ca2+ store vesicles (Huh
et al. 2006b; Yoo et al. 2005 , 2014 ). Hence, the CGB concentration in the small
nucleoplasmic vesicles will be at least several-fold higher than the estimated 80 μM,
the value given for the whole nucleus, and is most likely substantially higher than
200 μM CGB present in secretory granules.
In addition to the concentrations of CGB and the IP 3 Rs contained in the organ-
elles, the molecular contents and organization inside the organelles will also be of
crucial importance in the formation of the IP 3 -sensitive Ca2+ store properties of
respective Ca2+ store organelles. Although both secretory granules and the nucleo-
plasmic Ca2+ store vesicles contain CGB and the IP 3 Rs and release Ca2+ in response
to IP 3 , there appears to be a fundamental difference in the intrinsic functions between
the two organelles; while secretory granules store hormones and other essential
bioactive molecules in addition to high concentrations of Ca2+, the small nucleoplas-
mic Ca2+ store vesicles do not appear to store high concentrations of other bioactive
proteins, but rather appears to store primarily large amounts of Ca2+. In this respect,
the primary function of the nucleoplasmic Ca2+ store vesicles is thought to be Ca2+
storage/control in the nucleoplasm, which is consistent with the high IP 3 sensitivity
of the IP 3 R/Ca2+ channels in the nucleoplasm (Huh et al. 2007 ).
Conserved Nature of the Inositol 1,4,5-Trisphosphate Receptor and Chromogranin...