Regulation of cholecystokinin secretion by ATP-sensitive potassium channels

Abstract

The relationship of potassium channel activity to the secretion of cholecystokinin (CCK) was evaluated in STC-1 cells, an intestinal CCK-secreting cell line. Patch-clamp and 86Rb efflux studies showed that an ATP-sensitive potassium channel was endogenously expressed in STC-1 cells. Furthermore, channels are present in sufficient number to significantly modulate whole cell potassium permeability after either channel activation or closure with diazoxide (100 microM) or disopyramide (200 microM), respectively. Inhibition of channel activity with glucose (5-20 mM) was found to depolarize the plasma membrane, increase cytosolic calcium levels, and stimulate CCK release. Glucose-mediated release of CCK, as well as the increase in cytosolic calcium, was inhibited by the calcium channel blocker diltiazem (10 microM). It is concluded that intestinal secretion of CCK may be tonically controlled by activity of basally active ATP-sensitive potassium channels, and after inhibition of channel activity, calcium-dependent CCK secretion is stimulated.

Studies with GIP/Ins cells indicate secretion by gut K cells is KATPchannel independent

“…Patch-clamp studies have also demonstrated the presence of K ATP channels in parent STC-1 cells (2,28,30,58). Thus it has been proposed that they play a role in regulating CCK secretion (2,27,28). However, the results presented in this paper suggest that K ATP channels play, at best, a very minor role in regulating CCK secretion, since CCK-producing cells in vivo do not express detectable levels of Kir 6.1 or Kir 6.2.…”

“…This conclusion is consistent with our in vivo immunohistochemical studies indicating that gut L cells, like gut K cells, do not express detectable Kir 6.1 or Kir 6.2. Patch-clamp studies have also demonstrated the presence of K ATP channels in parent STC-1 cells (2,28,30,58). Thus it has been proposed that they play a role in regulating CCK secretion (2,27,28).…”

“…All cells were cultured in an atmosphere of 5% CO2-95% air and 100% humidity. MIN6 cells (passage [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] were cultured in DMEM containing 15% FCS, as previously described (39,67), and GIP/Ins cells were cultured in DMEM containing 10% FCS (39).…”

Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells

“…The identification of Kir6.2 and SUR1 by RT-PCR is consistent with the electrophysiological finding that the channels were sensitive to tolbutamide and diazoxide. K ATP channels have been detected previously in the poorly differentiated and multipotential CCK-secreting cell line STC-1, which also releases GIP and GLP-1 (31)(32)(33). CCK secretion from STC-1 cells was stimulated by 5 and 25 mmol/l glucose and by the nonspecific channel blocker disopyramide (31).…”

The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to l-phenylalanine in acutely isolated intestinal I cells

“…ATP-sensitive K ϩ channels regulating basal membrane potential (20,23) can be affected by CaSR. However, there was no difference in basal secretion between CaSR WT and KO CCK-eGFP cells.…”