Tài liệu Báo cáo khoa học: Synchronization of Ca2+ oscillations: a coupled oscillator-based

MINIREVIEW

Synchronization of Ca2+ oscillations: a coupled

oscillator-based mechanism in smooth muscle

Mohammad S. Imtiaz1

, Pierre-Yves von der Weid1 and Dirk F. van Helden2

1 Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada

2 School of Biomedical Sciences, University of Newcastle, Callaghan, NSW, Australia

Long-range signaling

Biological organs display coordinated activities that

can extend over large distances. The spatial extent of

signaling required for such long-distance coordination

is many orders of magnitude greater than the size of

the participating cells; for example, coordinated con￾tractions of the intestine can occur over 250 cm

lengths [1], whereas smooth muscle cells are small

(typical size range 50–200 lm [2]). The problem is

further exacerbated when one considers that millions

of cells, each with its own intrinsic rhythm, partici￾pate in this ‘mob action’, and yet a meaningful global

outcome emerges. It is fascinating that in systems

such as the gut, even isolated muscle tissue

preparations continue to show coordinated rhythmic

contractions in the absence of any external neural

control [3]; thus, in such systems, the synchronizing

mechanism is embedded within the rhythmically oscil￾lating cells themselves. In this article, we review a

long-range signaling mechanism in smooth muscle

that explains global outcomes of local interactions [4–

10]. The main feature of this signaling mechanism is

coupled oscillator-based synchronization of Ca2+

oscillations across cells, which drives membrane

potential changes and causes coordinated contrac￾tions. The key elements of this mechanism are a

Ca2+ release–refill cycle of endoplasmic reticulum ⁄

Keywords

Ca2+ oscillations; Ca2+ stores; coupled

oscillators; lymphatics; slow waves;

synchronization

Correspondence

M. S. Imtiaz, Department of Physiology &

Pharmacology, Faculty of Medicine,

University of Calgary, Health Sciences

Centre, 3330 Hospital Drive NW, Calgary,

Alberta T2N 4N1, Canada

Fax: +1 403 210 8195

Tel: +1 403 210 9838

E-mail: [email protected]

(Received 31 March 2009, revised

11 September 2009, accepted 14

October 2009)

doi:10.1111/j.1742-4658.2009.07437.x

Entrained oscillations in Ca2+ underlie many biological pacemaking phe￾nomena. In this article, we review a long-range signaling mechanism in

smooth muscle that results in global outcomes of local interactions. Our

results are derived from studies of the following: (a) slow-wave depolariza￾tions that underlie rhythmic contractions of gastric smooth muscle; and (b)

membrane depolarizations that drive rhythmic contractions of lymphatic

smooth muscle. The main feature of this signaling mechanism is a coupled

oscillator-based synchronization of Ca2+ oscillations across cells that

drives membrane potential changes and causes coordinated contractions.

The key elements of this mechanism are as follows: (a) the Ca2+ release–

refill cycle of endoplasmic reticulum Ca2+ stores; (b) Ca2+-dependent

modulation of membrane currents; (c) voltage-dependent modulation of

Ca2+ store release; and (d) cell–cell coupling through gap junctions or

other mechanisms. In this mechanism, Ca2+ stores alter the frequency of

adjacent stores through voltage-dependent modulation of store release.

This electrochemical coupling is many orders of magnitude stronger than

the coupling through diffusion of Ca2+ or inositol 1,4,5-trisphosphate, and

thus provides an effective means of long-range signaling.

Abbreviations

[Ca2+]c, cytosolic Ca2+ concentration; 18-b-GA, 18-b-glycyrrhetinic acid; ICC, interstitial cell of Cajal; Ins(1,4,5)P3, inositol 1,4,5-trisphosphate.

278 FEBS Journal 277 (2010) 278–285 ª 2009 The Authors Journal compilation ª 2009 FEBS