Cell Calcium 39 (2006) 197–208
Anti-phase calcium oscillations in astrocytes via
inositol (1, 4, 5)-trisphosphate regeneration
Ghanim Ullah
a,∗
, Peter Jung
a
, A.H. Cornell-Bell
b
a
Department of Physics and Astronomy and Quantitive Biology Institute,
Ohio University, Athens, OH 45701, USA
b
Anscans LLC, Ivoryton, CT, USA
Received 18 July 2005; received in revised form 22 October 2005; accepted 26 October 2005
Available online 2 December 2005
Abstract
Observations in cultured mouse astrocytes suggest anti-phase synchronization of cytosolic calcium concentrations in nearest neighbor cells
that are coupled through gap junctions. A mathematical model is used to investigate physiologic conditions under which diffusion of the
second messenger inositol (1, 4, 5)-trisphosphate (IP
3
) through gap junctions can facilitate synchronized anti-phase Ca
2+
oscillations. Our
model predicts anti-phase oscillations in both cytosolic calcium and IP
3
concentrations if (a) the gap junction permeability is within a window
of values and (b) IP
3
is regenerated in the astrocytes via, e.g. phospholipase C
. This result sheds new light on the current dispute on the
mechanism of intercellular calcium signaling. It provides indirect evidence for a partially regenerative mechanism as the model excludes
anti-phase synchrony in the absence of IP
3
regeneration.
© 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Calcium signaling is one of the most frequently observed
intracellular signaling mechanisms (for a comprehensive
review see [1]). Calcium is released from internal stores,
most notably the endoplasmic reticulum, through inositol
(1, 4, 5)-trisphosphate receptors (IP
3
Rs) activated by inositol
(1, 4, 5)-trisphosphate (IP
3
). As Ca
2+
is released, it activates
nearby IP
3
Rs through Ca
2+
induced Ca
2+
release, triggering
an intracellular Ca
2+
wave propagating through the cell. In
many cases, Ca
2+
signals can also propagate across the cell
membrane to form what has been termed an intercellular
Ca
2+
wave. The coupling mechanism, however, varies
between the cell-types. Pancreatic acinar cells are connected
by Cx32- and Cx26-built gap-junctional channels. Yule et
al. [2] have shown that these gap junctions are permeable to
IP
3
and Ca
2+
. Through mathematical modeling it has been
∗
Corresponding author. Tel.: +1 740 593 9671; fax: +1 740 593 0433.
E-mail address: ghanimul@helios.phy.ohiou.edu (G. Ullah).
shown that the Ca
2+
coupling, enhanced by IP
3
diffusion
leveling the IP
3
concentrations between the cells, can lead
to in-phase and anti-phase synchronization of Ca
2+
and
propagating Ca
2+
waves [3].
In astrocytes, however, the situation is different. In astro-
cytes the gap junctions are build by Cx43 [4,5]. Numerous
observations indicate that Ca
2+
cannot be the main messenger
of the Ca
2+
waves across the cells although there may exists
a small conductance for Ca
2+
. Carter et al. [6], have shown
that the gap junctions composed of Cx43 in aortic endothe-
lial cells are extensively permeable to IP
3
. Intercellular Ca
2+
waves propagate with or without exhibiting a Ca
2+
response;
if the intracellular Ca
2+
response is reduced pharmacologi-
cally, its propagation range is not affected [7]. Intracellular
Ca
2+
waves propagate through cells where calcium-induced
calcium release is inhibited [7]. In the absence of IP
3
loading
astrocytes with an elevated Ca
2+
concentration do not initiate
a Ca
2+
wave. Another observation suggesting that Ca
2+
is not
the main signaling molecule is that intercellular Ca
2+
waves
only travel a finite distance (about 300 m). If Ca
2+
would be
the messenger, such an abortive wave would not be expected.
0143-4160/$ – see front matter © 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ceca.2005.10.009