Sodium current in human intestinal interstitial cells of Cajal.
Interstitial cells of Cajal (ICC) generate the electrical slow wave required for normal gastrointestinal motility. The ionic conductances expressed in human intestinal ICC are unknown. The aim of this study was to determine expression of a Na+ current in human intestinal ICC and to determine the effects of the Na+ current on the slow wave. Visually identified, freshly dissociated, single ICC were verified by the presence of c-kit mRNA by using single-cell RT-PCR. Standard whole cell currents were recorded from patch-clamped ICC held at -100 mV between pulse protocols. A Na+ current was identified in human intestinal ICC. The current activated at -55 mV and peaked at -30 mV. Extracellular N-methyl-d-glucamine abolished and QX-314 (500 microM) blocked the Na+ current, but nifedipine and Ni2+ did not. The Na+ current was activated by shear stress. Single-cell RT-PCR detected mRNA for the Na+ alpha-subunit SCN5A in single human intestinal ICC. Lidocaine (200 microm) and QX-314 (500 microM) decreased slow wave frequency, and stretch increased slow wave frequency. A mechanosensitive Na+ channel current is present in human intestinal ICC and appears to play a role in the control of intestinal motor function.
Strege
Peter R
PR
Enteric Neuroscience Program, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Ou
Yijun
Y
Sha
Lei
L
Rich
Adam
A
Gibbons
Simon J
SJ
Szurszewski
Joseph H
JH
Sarr
Michael G
MG
Farrugia
Gianrico
G
D004553:Electric Conductivity; D006801:Humans; D066298:In Vitro Techniques; D007477:Ions; D007583:Jejunum / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000502:physiology*; D013314:Stress, Mechanical; D013997:Time Factors
D007477:Ions; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium