Tetrodotoxin-insensitive sodium channels in a cardiac cell line from a transgenic mouse.
The electrophysiological properties of a cardiac cell line (MCM1) originating from a transgenic mouse were characterized. The dominant current in these cells is a sodium current that is insensitive to concentrations of tetrodotoxin (TTX) up to 100 microM. It activates and inactivates rapidly with half-maximal activation at -40 mV and half-maximal inactivation at -79 mV. This sodium current is reduced by agents that increase intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and activate cAMP-dependent protein kinase including isoproterenol, 8-bromo-cAMP, and isobutylmethylxanthine. The phenylalkylamine desmethoxyverapamil blocks the TTX-insensitive sodium current in MCM1 cells in both tonic and use-dependent fashion. Membrane depolarization enhances this block. It is proposed that the TTX-insensitive sodium current in these cells may be similar in origin to the embryonic type of TTX-insensitive sodium current described in other cardiac and skeletal muscle preparations.
Department of Pharmacology, University of Washington, Seattle 98195.
A
A
Sculptoreanu
M
M
Morton
C L
CL
Gartside
S D
SD
Hauschka
W A
WA
Catterall
T
T
Scheuer
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014700:Verapamil / Q000031:analogs & derivatives / Q000494:pharmacology
D015222:Sodium Channels; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013779:Tetrodotoxin; C043184:4-desmethoxyverapamil; D014700:Verapamil; D000242:Cyclic AMP; D011494:Protein Kinases; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine