Secretin-regulated chloride channel on the apical plasma membrane of pancreatic duct cells

Abstract

Using the patch clamp technique we have identified a small conductance ion channel that typically occurs in clusters on the apical plasma membrane of pancreatic duct cells. The cell-attached current/voltage (I/V) relationship was linear and gave a single channel conductance of about 4 pS. Since the reversal potential was close to the resting membrane potential of the cell, and unaffected by changing from Na+-rich to K+-rich pipette solutions, the channel selects for anions over cations in cell-attached patches. The open state probability was not voltage-dependent. Adding 25 mM-bicarbonate to the bath solution caused a slight outward rectification of the I/V relationship, but otherwise, the characteristics of the channel were unaffected. In excised, inside-out, patches the I/V relationship was linear and gave a single channel conductance of about 4 pS. A threefold chloride concentration gradient across the patch (sulphate replacement) shifted the single channel current reversal potential by -26 mV, indicating that the channel is chloride selective. Stimulation of duct cells with secretin (10 nM), dibutyryl cyclic AMP (1 mM) and forskolin (1 microM) increased channel open state probability and also increased the number of channels, and/or caused disaggregation of channel clusters, in the apical plasma membrane. Coupling of this channel to a chloride/bicarbonate exchanger would provide a mechanism for electrogenic bicarbonate secretion by pancreatic duct cells.