Philos Transact A Math Phys Eng Sci. 2006 May 15;364(1842):1135-54. A mathematical model of pacemaker activity recorded from mouse small intestine. Youm JB, Kim N, Han J, Kim E, Joo H, Leem CH, Goto G, Noma A, Earm YE. College of Medicine, 2020 Cardiovascular Institute, Inje University Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics Busan 614-735, South Korea. The pacemaker activity of interstitial cells of Cajal (ICCs) has been known to initiate the propagation of slow waves along the whole gastrointestinal tract through spontaneous and repetitive generation of action potentials. We studied the mechanism of the pacemaker activity of ICCs in the mouse small intestine and tested it using a mathematical model. The model includes ion channels, exchanger, pumps and intracellular machinery for Ca(2+) regulation. The model also incorporates inositol 1,4,5-triphosphate (IP(3)) production and IP(3)-mediated Ca(2+) release activities. Most of the parameters were obtained from the literature and were modified to fit the experimental results of ICCs from mouse small intestine. We were then able to compose a mathematical model that simulates the pacemaker activity of ICCs. The model generates pacemaker potentials regularly and repetitively as long as the simulation continues. The frequency was set at 20min(-1) and the duration at 50% repolarization was 639ms. The resting and overshoot potentials were -78 and +1.2mV, respectively. The reconstructed pacemaker potentials closely matched those obtained from animal experiments. The model supports the idea that cyclic changes in [Ca(2+)](i) and [IP(3)] play key roles in the generation of ICC pacemaker activity in the mouse small intestine. ================================================================================================ 1: Philos Transact A Math Phys Eng Sci. 2006 May 15;364(1842):1223-43. Links Simulation of Ca(2+)-activated Cl(-) current of cardiomyocytes in rabbit pulmonary vein: implications of subsarcolemmal Ca(2+) dynamics. Leem CH, Kim WT, Ha JM, Lee YJ, Seong HC, Choe H, Jang YJ, Youm JB, Earm YE. University of Ulsan College of Medicine Department of Physiology 388-1 Poongnap-Dong Songpa-Ku, Seoul 138-736, South Korea. In recent studies, we recorded transiently activated outward currents by the application of three-step voltage pulses to induce a reverse mode of Na(+)-Ca(2+) exchange (NCX). We found that these currents were mediated by a Ca(2+)-activated Cl(-) current. Based on the recent reports describing the atrial Ca(2+) transients, the Ca(2+) transient at the subsarcolemmal space was initiated and then diffused into the cytosolic space. Because the myocardium in the pulmonary vein is an extension of the atrium, the Ca(2+)-activated Cl(-) current may reflect the subsarcolemmal Ca(2+) dynamics. We tried to predict the subsarcolemmal Ca(2+) dynamics by simulating these current traces. According to recent reports on the geometry of atrial myocytes, we assumed that there were three compartments of sarcoplasmic reticulum (SR): a network SR, a junctional SR and a central SR. Based on these structures, we also divided the cytosolic space into three compartments: the junctional, subsarcolemmal and cytosolic spaces. Geometry information and cellular capacitance suggested that there were essentially no T-tubules in these cells. The basic physical data, such as the compartmental volumes, the diffusion coefficients and the stability coefficients of the Ca(2+) buffers, were obtained from the literature. In the simulation, we incorporated the NCX, the L-type Ca(2+) channel, the rapid activating outward rectifier K(+) channel, the Na(+)-K(+) pump, the SR Ca(2+)-pump, the ryanodine receptor, the Ca(2+)-activated Cl(-) channel and the dynamics of Na(+), K(+), Ca(2+) and Cl(-). In these conditions, we could successfully reconstruct the Ca(2+)-activated Cl(-) currents. The simulation allowed estimation of the Ca(2+) dynamics of each compartment and the distribution of the Ca(2+)-activated Cl(-) channel and the NCX in the sarcolemma on the junctional or subsarcolemmal space.