title: Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies.
abstract: Patch-clamp recordings in single-cell expression systems have been traditionally used to study the function of ion channels. However, this experimental setting does not enable assessment of tissue-level function such as action potential (AP) conduction. Here we introduce a biosynthetic system that permits studies of both channel activity in single cells and electrical conduction in multicellular networks. We convert unexcitable somatic cells into an autonomous source of electrically excitable and conducting cells by stably expressing only three membrane channels. The specific roles that these expressed channels have on AP shape and conduction are revealed by different pharmacological and pacing protocols. Furthermore, we demonstrate that biosynthetic excitable cells and tissues can repair large conduction defects within primary 2- and 3-dimensional cardiac cell cultures. This approach enables novel studies of ion channel function in a reproducible tissue-level setting and may stimulate the development of new cell-based therapies for excitable tissue repair.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Kirkton
authors.forename: Nenad
authors.initials: N
authors.lastname: Bursac
mesh_terms: D000200:Action Potentials; D002460:Cell Line; D064987:Cell- and Tissue-Based Therapy; D004553:Electric Conductivity; D004558:Electric Stimulation; D055664:Electrochemical Techniques; D005818:Genetic Engineering / Q000379:methods*; D006321:Heart / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D010957:Plasmids; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D007473:Ion Channels