title: Modeling of stochastic behavior of pacemaker potential in interstitial cells of Cajal.
abstract: It is widely accepted that interstitial cells of Cajal (ICCs) generate pacemaker potentials to propagate slow waves along the whole gastrointestinal tract. Previously, we constructed a biophysically based model of ICCs in mouse small intestine to explain the pacemaker mechanism. Our previous model, however, could not explain non-uniformity of pacemaker potentials and random occurrence of unitary potentials, thus we updated our model. The inositol 1,4,5-trisphosphate (IP3)-mediated Ca(2+) mobilization is a key event to drive the cycle of pacemaker activity and was updated to reproduce its stochastic behavior. The stochasticity was embodied by simulating random opening and closing of individual IP3-mediated Ca(2+) channel. The updated model reproduces the stochastic features of pacemaker potentials in ICCs. Reproduced pacemaker potentials are not uniform in duration and interval. The resting and peak potentials are -75.5 ± 1.1 mV and -0.8 ± 0.5 mV, respectively (n = 55). Frequency of pacemaker potential is 14.3 ± 0.4 min(-1) (n = 10). Width at half-maximal amplitude of pacemaker potential is 902 ± 6 ms (n = 55). There are random events of unitary potential-like depolarization. Finally, we compared our updated model with a recently published model to speculate which ion channel is the best candidate to drive pacemaker depolarization. In conclusion, our updated mathematical model could now reproduce stochastic features of pacemaker activity in ICCs.
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea. Electronic address: youmjb@inje.ac.kr.
authors.forename: Jae Boum
authors.initials: JB
authors.lastname: Youm
authors.affiliation: Department of Physiology University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Chae Hun
authors.initials: CH
authors.lastname: Leem
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: Sung Ryul
authors.initials: SR
authors.lastname: Lee
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: In-Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Heo
authors.affiliation: Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, South Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, South Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D013269:Stochastic Processes
chemical_list: D015220:Calcium Channels; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium
keywords: Inositol 1,4,5-trisphosphate receptor; Interstitial cells of Cajal; Mouse small intestine; Pacemaker activity; Stochastic integration