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NEUROREGULATION AND MOTILITY
Intestinal Disease Research Programme, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Submitted 9 July 2004 ; accepted in final form 1 November 2004
Cl– channels are proposed to play a role in gut pacemaker activity, but little is known about the characteristics of Cl– channels in interstitial cells of Cajal (ICC), the intestinal pacemaker cells. The objective of the present study was to identify whole cell Cl– currents in ICC associated with previously observed single-channel activity and to characterize its inward rectification. Whole cell patch-clamp studies showed that ICC express an inwardly rectifying Cl– current that was not sensitive to changes in cation composition of the extracellular solutions. Currents were not affected by replacing all cations with N-methyl-D-glucamine (NMDG+). Whole cell currents followed the Cl– equilibrium potential and were inhibited by DIDS and 9-anthracene carboxylic acid. Ramp protocols of single-channel activity showed that inward rectification was due to reduction in single-channel open probability, not a reduction in single-channel conductance. Single-channel data led to the hypothesis that strong cooperation exists between 30-pS channels that show less cooperation at potentials positive to the reversal potential. Hence, an inwardly rectifying Cl– channel plays a prominent role in determining pacemaker activity in the gut.
pacemaking activity; gastrointestinal motility; interstitial cells of Cajal
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