J. Ramosfranco et al., ISOFORM-SPECIFIC FUNCTION OF SINGLE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR CHANNELS, Biophysical journal, 75(2), 1998, pp. 834-839
The inositol 1,4,5-trisphosphate receptor (InsP(3)R) family of Ca2+ re
lease channels is central to intracellular Ca2+ signaling in mammalian
cells. The InsP(3)R channels release Ca2+ from intracellular compartm
ents to generate localized Ca2+ transients that govern a myriad of cel
lular signaling phenomena (Berridge, 1993, Nature. 361:315-325; Joseph
, 1996, Cell Signal. 8:1-7; Kume et al,, 1997, Science. 278:1940-1943;
Berridge, 1997, Nature. 368:759-760), Most cells express multiple Ins
P(3)R isoforms, but only the function of the single type 1 InsP(3)R ch
annel is known. Here the single-channel function of single type 2 InsP
(3)R channel is defined for the first time. The type 2 InsP(3)R forms
channels with permeation properties similar to that of the type 1 rece
ptor. The InsP(3) regulation and Ca2+ regulation of type 1 and type 2
InsP(3)R channels are strikingly different. Both InsP(3) and Ca2+ are
more effective at activating single type 2 InsP(3)R, indicating that s
ingle type 2 channels mobilize substantially more Ca2+ than single typ
e 1 channels in cells. Furthermore, high cytoplasmic Ca2+ concentratio
ns inactivate type 1, but not type 2, InsP(3)R channels. This indicate
s that type 2 InsP(3)R channel is different from the type 1 channel in
that its activity will not be inherently self-limiting, because Ca2passing through an active type 2 channel cannot feed back and turn the
channel off. Thus the InsP(3)R identity will help define the spatial
and temporal nature of local Ca2+ signaling events and may contribute
to the segregation of parallel InsP(3) signaling cascades in mammalian
cells.