Visualizing sodium dynamics in isolated cardiomyocytes using fluorescent nanosensors.
Regulation of sodium flux across the cell membrane plays a vital role in the generation of action potentials and regulation of membrane excitability in cells such as cardiomyocytes and neurons. Alteration of sodium channel function has been implicated in diseases such as epilepsy, long QT syndrome, and heart failure. However, single cell imaging of sodium dynamics has been limited due to the narrow selection of fluorescent sodium indicators available to researchers. Here we report, the detection of spatially defined sodium activity during action potentials. Fluorescent nanosensors that measure sodium in real-time, are reversible and are completely selective over other cations such as potassium that were used to image sodium. The use of the nanosensors in vitro was validated by determining drug-induced activation in heterologous cells transfected with the voltage-gated sodium channel Na(V)1.7. Spatial information of sodium concentrations during action potentials will provide insight at the cellular level on the role of sodium and how slight changes in sodium channel function can affect the entirety of an action potential.
Dubach
J Matthew
JM
Biomedical Engineering Group, The Charles Stark Draper Laboratory, 555 Technology Square, Cambridge, MA 02139, USA.
Das
Saumya
S
Rosenzweig
Anthony
A
Clark
Heather A
HA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D015374:Biosensing Techniques / Q000379:methods*; D002460:Cell Line; D002478:Cells, Cultured; D005453:Fluorescence; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D062556:NAV1.7 Voltage-Gated Sodium Channel; D036103:Nanotechnology / Q000379:methods*; D018408:Patch-Clamp Techniques; D051381:Rats; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D012964:Sodium