Taurodeoxycholate activates potassium and chloride conductances via an IP3-mediated release of calcium from intracellular stores in a colonic cell line (T84)

Abstract

Whole-cell patch-clamp techniques and fluorescence measurements of intracellular Ca2" concentration, (Ca2+)i, were used to investigate the mechanism oftaurodeoxycholate (TDC) stimulation of Cl-secretion in the T84 colonic cell line. During perforated whole-cell recordings, the cell membrane voltage was alternately clamped to EK and Ea. Initially, TDC (0.75 mM) stimulated inward nonselective cation currents that were composed of discrete large conductance single-channel events. This initial response was followed by activation of K+ and C0-currents with peak values of385±41 pA and 98±28 pA, respectively (n = 12). The K+ and Cl-currents oscillated while TDC was present and returned to baseline levels upon its removal. The threshold for activation of the oscillatory currents was 0.1 mM TDC. Taurocholate TDC-induced (Ca2")i oscillations were observed in the absence of bath Ca2"; however, removal of bath Ca2" during the TDC response caused (Ca2+); to return to near baseline values. Simultaneous K+ current and (Ca2+)i measurements confirmed that the initial nonselective cation current was independent of (Ca2`)j, while K+ current oscillations were in phase with the (Ca2+)i oscillations. TDC induced inositol monophosphate (IP) accumulation, reflecting production of inositol 1,4,5-trisphosphate (IP3) during TDC stimulation. The response to TDC during standard whole-cell patch-clamp was similar to that observed with perforated whole-cell recordings, except the nonselective cation current was prolonged. When heparin (1 mg/ml) was added to the pipette under these conditions, the Ca2-activated currents were inhibited, but the nonselective cat- Clin. Invest. 1993. 92:2173-2181

Phosphatidylinositol 3-kinase facilitates bile acid-induced Ca2+responses in pancreatic acinar cells

“…The exact mechanisms of bile acid-induced pancreatitis in experimental models (1,17) are not well established and are thought to be through their "blunt" effect as detergents. However, data acquired in different cell types, including the pancreatic acinar cell, have indicated that bile acids regulate specific cellular signals, in particular, [Ca 2ϩ ] i responses (8,13,14,25,31,34). These data also demonstrated a possible role of PI3K in bile acid-induced signaling pathways.…”

Bile Acids Enhance Invasiveness of Cryptosporidium spp. into Cultured Cells

“…We have shown that the presence of NaTC in the solution containing freshly excysted sporozoites increased the soluble protein content, which may be due to enhanced apical organelle discharge. Apical organelle discharge of C. parvum is calcium dependent (6), and the induction of calcium signaling by bile salts has been well-documented in mammalian cells (7,13,25). Whether or not bile salts induce calcium signaling in C. parvum or other Apicomplexa remains to be determined.…”

Mast cells and histamine contribute to bile acid-stimulated secretion in the mouse colon.

“…Were such binding to occur, the basolateral membrane might be exposed to a much lower intracellular concentration than that present when CDCA was added to the serosal compartment. The entry of CDCA into the colonic enterocyte is likely to cause acidification of the cell (36), as well as calcium mobilization (22)(23)(24), and both of these might contribute to an increase in paracellular permeability. If this occurs, CDCA would also enter the mucosa via the paracellular pathway and interact directly with the basolateral membrane of the enterocytes, as well as with mast cells.…”

“…These include direct mucosal injury (7,12); enhancement of mucosal permeability (7,16,17); and stimulation of cAMP production ( 16,18,19), mucosal prostaglandin synthesis (20,21), calcium influx and calcium release from intracellular stores in epithelial cells (22)(23)(24), and local neural enteric reflexes (25). A secretory effect of conjugated bile acids when applied mucosally is observed only in association with an increase in permeability (26,27), suggesting that enhancement of mucosal permeability may be necessary to permit access for these large, charged molecules to the basolateral membrane and/or to the subepithelium, where they then can exert their secretory effect.…”