Sodium current in human jejunal circular smooth muscle cells.
OBJECTIVE
Sodium channels are key regulators of neuronal and muscle excitability. However, sodium channels have not been definitively identified in gastrointestinal smooth muscle. The aim of the present study was to determine if a Na(+) current is present in human jejunal circular smooth muscle cells.


METHODS
Currents were recorded from freshly dissociated cells using patch-clamp techniques. Complementary DNA (cDNA) libraries constructed from the dissociated cells were screened to determine if a message for alpha subunits of Na(+) channels was expressed. Smooth muscle cells were also collected using laser-capture microdissection and screened.


RESULTS
A tetrodotoxin-insensitive Na(+) channel was present in 80% of cells patch-clamped. Initial activation was at -65 mV with peak inward current at -30 mV. Steady-state inactivation and activation curves revealed a window current between -75 and -60 mV. The Na(+) current was blocked by lidocaine and internal and external QX314. A cDNA highly homologous to SCN5A, the alpha subunit of the cardiac Na(+) channel, was present in the cDNA libraries constructed from dissociated cells and from smooth muscle cells collected using laser-capture microdissection.


CONCLUSIONS
Human jejunal circular smooth muscle cells express a tetrodotoxin-insensitive Na(+) channel, probably SCN5A. Whether SCN5A plays a role in the pathophysiology of human gut dysmotilities remains to be determined.
Holm
Adrian N
AN
Department of Physiology and Biophysics, Enteric NeuroScience Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Rich
Adam
A
Miller
Steven M
SM
Strege
Peter
P
Ou
Yijun
Y
Gibbons
SimonJ
S
Sarr
Michael G
MG
Szurszewski
Joseph H
JH
Rae
James L
JL
Farrugia
Gianrico
G
D000779:Anesthetics, Local / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology; D006801:Humans; D007583:Jejunum / Q000166:cytology / Q000502:physiology*; D007700:Kinetics; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D062554:NAV1.5 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C568320:SCN5A protein, human; D015222:Sodium Channels; D013779:Tetrodotoxin; D008012:Lidocaine; D012964:Sodium; D009543:Nifedipine