High-conductance chloride channels generate pacemaker currents in interstitial cells of Cajal. 2002

Jan D Huizinga, and Yaohui Zhu, and Jing Ye, and Areles Molleman
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. huizinga@mcmaster.ca

OBJECTIVE Interstitial cells of Cajal (ICCs) are responsible for slow, wave-driven, rhythmic, peristaltic motor patterns in the gastrointestinal tract. The aim was to identify and characterize the ion channels that generate the underlying pacemaker activity. METHODS Single ion channel recordings were obtained from nonenzymatically isolated ICCs and studied by using the cell attached and inside-out configurations of the patch clamp technique. RESULTS A high-conductance chloride channel was observed in ICCs that was spontaneously and rhythmically active at the same frequency as the rhythmic inward currents defining ICC pacemaker activity, 20-30 cycles/min at room temperature. Main conductance levels occurred between 122-144 pS and between 185-216 pS. Periodicity in the channel opening coincided with periodicity in membrane potential change, hence, at the single channel level, chloride channels were seen to be associated with the generation of rhythmic changes in membrane potential. CONCLUSIONS ICCs harbor high-conductance chloride channels that participate in the generation of pacemaker activity and may become a target for pharmacologic treatment of gut motor disorders.

UI MeSH Term Description Entries
D007583 Jejunum The middle portion of the SMALL INTESTINE, between DUODENUM and ILEUM. It represents about 2/5 of the remaining portion of the small intestine below duodenum. Jejunums
D010507 Periodicity The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). Cyclicity,Rhythmicity,Biological Rhythms,Bioperiodicity,Biorhythms,Biological Rhythm,Bioperiodicities,Biorhythm,Cyclicities,Periodicities,Rhythm, Biological,Rhythmicities,Rhythms, Biological
D011336 Probability The study of chance processes or the relative frequency characterizing a chance process. Probabilities
D004553 Electric Conductivity The ability of a substrate to allow the passage of ELECTRONS. Electrical Conductivity,Conductivity, Electric,Conductivity, Electrical
D005453 Fluorescence The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001683 Biological Clocks The physiological mechanisms that govern the rhythmic occurrence of certain biochemical, physiological, and behavioral phenomena. Biological Oscillators,Oscillators, Endogenous,Pacemakers, Biological,Biologic Clock,Biologic Oscillator,Biological Pacemakers,Clock, Biologic,Clocks, Biological,Oscillator, Biologic,Oscillators, Biological,Pacemaker, Biologic,Pacemakers, Biologic,Biologic Clocks,Biologic Oscillators,Biologic Pacemaker,Biologic Pacemakers,Biological Clock,Biological Oscillator,Biological Pacemaker,Clock, Biological,Clocks, Biologic,Endogenous Oscillator,Endogenous Oscillators,Oscillator, Biological,Oscillator, Endogenous,Oscillators, Biologic,Pacemaker, Biological
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018118 Chloride Channels Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN. CaCC,Calcium-Activated Chloride Channel,Chloride Ion Channel,Chlorine Channel,Ion Channels, Chloride,CaCCs,Calcium-Activated Chloride Channels,Chloride Channel,Chloride Ion Channels,Chlorine Channels,Ion Channel, Chloride,Calcium Activated Chloride Channel,Calcium Activated Chloride Channels,Channel, Calcium-Activated Chloride,Channel, Chloride,Channel, Chloride Ion,Channel, Chlorine,Channels, Calcium-Activated Chloride,Channels, Chloride,Channels, Chloride Ion,Channels, Chlorine,Chloride Channel, Calcium-Activated,Chloride Channels, Calcium-Activated
D018408 Patch-Clamp Techniques An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used. Patch Clamp Technique,Patch-Clamp Technic,Patch-Clamp Technique,Voltage-Clamp Technic,Voltage-Clamp Technique,Voltage-Clamp Techniques,Whole-Cell Recording,Patch-Clamp Technics,Voltage-Clamp Technics,Clamp Technique, Patch,Clamp Techniques, Patch,Patch Clamp Technic,Patch Clamp Technics,Patch Clamp Techniques,Recording, Whole-Cell,Recordings, Whole-Cell,Technic, Patch-Clamp,Technic, Voltage-Clamp,Technics, Patch-Clamp,Technics, Voltage-Clamp,Technique, Patch Clamp,Technique, Patch-Clamp,Technique, Voltage-Clamp,Techniques, Patch Clamp,Techniques, Patch-Clamp,Techniques, Voltage-Clamp,Voltage Clamp Technic,Voltage Clamp Technics,Voltage Clamp Technique,Voltage Clamp Techniques,Whole Cell Recording,Whole-Cell Recordings

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