Calcium-associated mechanisms in gut pacemaker activity.
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A considerable body of evidence has revealed that interstitial cells of Cajal (ICC), identified with c-Kit-immunoreactivity, act as gut pacemaker cells, with spontaneous Ca(2+) activity in ICC as the probable primary mechanism.Namely, intracellular (cytosolic) Ca(2+) oscillations in ICC periodically activate plasmalemmal Ca(2+)-dependent ion channels and thereby generate pacemaker potentials.This review will, thus, focus on Ca(2+)-associated mechanisms in ICC in the gastrointestinal (GI) tract, including auxiliary organs.
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Affiliation: Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. h44673a@nucc.cc.nagoya-u.ac.jp
ABSTRACT
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A considerable body of evidence has revealed that interstitial cells of Cajal (ICC), identified with c-Kit-immunoreactivity, act as gut pacemaker cells, with spontaneous Ca(2+) activity in ICC as the probable primary mechanism. Namely, intracellular (cytosolic) Ca(2+) oscillations in ICC periodically activate plasmalemmal Ca(2+)-dependent ion channels and thereby generate pacemaker potentials. This review will, thus, focus on Ca(2+)-associated mechanisms in ICC in the gastrointestinal (GI) tract, including auxiliary organs. |
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fig02: ICC [Ca2+]i oscillations synchronized with mechanical (A) and electrical (B) activities in cell cluster preparations isolated from the muscle layer of the murine small intestine. This figure was made by modifying Figure 2 of [44] and Figure 4 of [27]. (A): Ca2+ images (fluo-3 fluorescence) obtained from a cell cluster preparation with a high intensity area that could be used to monitor mechanical activity. Panels (a) and (b) are pseudo-colour Ca2+ images acquired at basal and peak times of an initial oscillation cycle in normal solution, respectively. The mechanical activity (c: movement) was estimated by tracking the high intensity area indicated by the arrow in (a). The time course of [Ca2+]i oscillations (d) was measured in the square region (red line) of the cell cluster preparation shown in (a). After this recording, using a K+ channel opener to suppress smooth muscle activity, we confirmed that ICC produced the Ca2+ activity in the square region [44]. The fluorescence is expressed relative to that at the initial basal time: Ft/F0.(B) Field potential (a) and fluo-4 fluorescence (b) were measured simultaneously in a cell cluster preparation in the presence of nifedipine which differentiates ICC activity by suppressing smooth muscle activity [27]. Thick and thin lines in (b) represent ICC and non-ICC regions of a cell cluster preparation, respectively. Mentions: Using cell cluster preparations from the murine small intestine, Torihashi et al.[27] and Nakayama et al.[23] recorded [Ca2+]i oscillations synchronized with spontaneous electrical and mechanical activities (Fig. 2). These results agree well with the hypothesis that [Ca2+]i oscillations in ICC generate pacemaker electrical activity by periodically activating Ca2+-activated ion channels in the plasma membrane (Scenario 1 in Fig. 3). Moreover, in guinea-pig and mouse stomach ICC, [Ca2+]i oscillations appear to be associated with spontaneous electrical and mechanical activities [26,54–56]. |
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Affiliation: Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. h44673a@nucc.cc.nagoya-u.ac.jp