The amiloride inhibitable Na+ conductance of rat colonic crypt cells is suppressed by forskolin

Previously we have shown that mid crypt cells of corticoid treated rats possess an amiloride inhibitable Na+ conductance (NAC) and show an increased Cl- conductance when stimulated by prostaglandin or the second messenger cAMP. The NAC is supposed to determine the magnitude of NaCl absorption. The Cl- conductance defines the magnitude of NaCl secretion. In the present whole cell (WC) patch clamp study we have examined whether the amiloride (3 mu mol/l) inhibitable NAC is downregulated when the Cl- conductance is increased by forskolin (5 mu mol/l, n = 20) or the phosphodiesterase inhibitor IBMX (1 mmol/l, n = 5). Under control conditions the amiloride inhibitable NAC was 2.7 +/- 0.4 nS. Forskolin depolarized the voltage from -58 +/- 2.0 to -48 +/- 1.9 mV and enhanced the WC conductance by 3.25 +/- 0.6 nS in these cells. The amiloride inhibitable NAC was reduced to 0.38 +/- 0.2 nS. These data confirm that forskolin enhances the Cl- conductance in these cells and they show for the first time that the Na+ conductance is reduced simultaneously. Thus the cells are able to change the direction of NaCl transport from absorption to secretion.