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.
Ecke
D
D
Physiologisches Institut der Albert-Ludwigs-Universitat, Hermann-Herder-Strasse 7, D-79104 Freiburg i.Br., Germany.
Bleich
M
M
Greger
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D004553:Electric Conductivity; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D018118:Chloride Channels; D002712:Chlorides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D005576:Colforsin; D000584:Amiloride; D012964:Sodium; D015056:1-Methyl-3-isobutylxanthine