The properties of the secretagogue-evoked chloride current in mouse pancreatic acinar cells

Abstract

In this paper we describe the properties of the secretagogue-evoked chloride current from mouse pancreatic acinar cells. Single cells were patch-clamped in the whole-cell configuration with solutions that excluded cation currents and then stimulated with 1 mM carbachol (CCh). This resulted in a current that rose to a peak and then decayed to a plateau level. The current/voltage relationship of the peak current was linear whereas that of the plateau phase was rectified and showed time and voltage dependence. To determine if the CCh evoked current was strictly Ca2+ dependent, we compared the properties of the plateau current with those of currents evoked by directly raising cytosolic [Ca2+] The properties of the two currents were the same, with both currents showing outward rectification, development at depolarised potentials, similar time constants of activation, permeability sequences and sensitivity to the Cl- channel inhibitor 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulphonic acid (DIDS). We conclude that the agonist-evoked rise in Ca2+ is alone a sufficient signal to activate the CL- current.

Paclitaxel Affects Cytosolic Calcium Signals by Opening the Mitochondrial Permeability Transition Pore

“…Since the Cl (Ca) channels are primarily under the control of cytosolic Ca 2ϩ (20) this suggests that paclitaxel elicits a Ca 2ϩ signal. To test this directly we carried out Ca 2ϩ imaging experiments using the Ca 2ϩ -sensitive fluorescent dye Calcium Green introduced into the cell cytosol via infusion through the solution of the patch pipette (21).…”

Ca2+ dynamics in salivary acinar cells: distinct morphology of the acinar lumen underlies near-synchronous global Ca2+ responses

“…Fluid secretion is, in the first instance, instigated by the opening of apical Cl -channels but activation of a K + channel is required to maintain cell hyperpolarization and to provide a route for K + exit (Petersen, 1992;Hayashi et al, 1995;Takeo et al, 1998). Salivary acinar cells have a robust Ca 2+ -dependent K + conductance (Maruyama et al, 1983;Smith and Gallacher, 1992) and the fact that this is missing in rodent pancreatic acinar cells (Kidd and Thorn, 2001) may explain their weaker secretory response. The identity of the Ca 2+ -dependent K + channel, recruited during fluid secretion in salivary acinar cells, is not known (Hayashi et al, 1995) but most models of secretion would place the K + channel on the basal plasma membrane.…”

Inositol (1,4,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells

“…The current-voltage graph was produced using 1.5 second voltage steps from a holding potential of -30 mV to a range of potentials between -75 mV and +75 mV. The currents obtained showed the typical outward rectification for the Cl -currents of pancreatic acinar cells (Kidd and Thorn, 2001) and the current amplitude was recorded at the end of the voltage step. Cells were treated with 100 µM latrunculin B for at least 5 minutes before recording the current-voltage relationship.…”

“…This concentration of Ca 2+ is known to activate the Cl (Ca) channels maximally (Kidd and Thorn, 2001), and by stepping to a range of membrane potentials we produced current-voltage relationships in control cells and in cells treated with latrunculin B (Fig. 6E).…”