title: A biophysical model of electrical activity in human β-cells.
abstract: Electrical activity in pancreatic β-cells plays a pivotal role in glucose-stimulated insulin secretion by coupling metabolism to calcium-triggered exocytosis. Mathematical models based on rodent data have helped in understanding the mechanisms underlying the electrophysiological patterns observed in laboratory animals. However, human β-cells differ in several aspects, and in particular in their electrophysiological characteristics, from rodent β-cells. Hence, from a clinical perspective and to obtain insight into the defects in insulin secretion relevant for diabetes mellitus, it is important to study human β-cells. This work presents the first mathematical model of electrical activity based entirely on published ion channel characteristics of human β-cells. The model reproduces satisfactorily a series of experimentally observed patterns in human β-cells, such as spiking and rapid bursting electrical activity, and their response to a range of ion channel antagonists. The possibility of Human Ether-a-Go-Go-related- and leak channels as drug targets for diabetes treatment is discussed based on model results.
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy. pedersen@dei.unipd.it
authors.forename: Morten Gram
authors.initials: MG
authors.lastname: Pedersen
mesh_terms: D055592:Biophysical Phenomena / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003198:Computer Simulation; D004560:Electricity; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008954:Models, Biological; D015221:Potassium Channels / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D049990:Membrane Transport Modulators; D015221:Potassium Channels; D015222:Sodium Channels