Engineering prokaryotic channels for control of mammalian tissue excitability.

ABSTRACT: The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNa_v) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNa_v orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes. Engineered fibroblasts ('E-Fibs') retain stable functional properties following extensive subculture or differentiation into myofibroblasts and rescue conduction s

SUBMITTER: Nguyen HX 

PROVIDER: S-EPMC5071848 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature