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NEUROREGULATION AND MOTILITY

Inwardly rectifying chloride channel activity in intestinal pacemaker cells

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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