Pflügers Archiv

, Volume 420, Issue 3, pp 319–328

Activation of nonselective cation channels in the basolateral membrane of rat distal colon crypt cells by prostaglandin E2

  • Christiane Siemer
  • Heinz Gögelein
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands

DOI: 10.1007/BF00374465

Cite this article as:
Siemer, C. & Gögelein, H. Pflügers Arch (1992) 420: 319. doi:10.1007/BF00374465

Abstract

Ion channels in the basolateral membrane of colonic crypts were investigated with the patch-clamp technique during stimulation of secretion. Intact crypts were isolated from rat distal colon and the cell potential was recorded by addition of nystatin to the pipette solution. The cell resting potential in the base of the crypt was −74±1 mV (n=90). Addition of 100 μM carbachol to the bath resulted in a transient hyperpolarization by 9 mV, which was probably due to the opening of basolateral K+ channels. In contrast, application of prostaglandin E2 (PGE2, 1 nM−1 μM) caused a dose-dependent depolarization in the base of the crypt. With 1 μM PGE2 cells depolarized from -74±1 to −27±2 mV (n=26). Cell potential recordings in the midcrypt showed only a slight and transient depolarization after application of PGE2, whereas cells close to the surface of the crypt had no response. In the base of the crypt the PGE2-induced depolarization could be completely inhibited by addition of 50 μM flufenamic acid, a known blocker of nonselective cation channels. After substitution of all monovalent cations by N-methyl-D-glucamine in the bath, PGE2 had no significant effect on the cell potential. Cell-attached experiments with no nystatin in the patch pipette revealed the activation of ion channels in the basolateral membrane after application of PGE2. After excision of the membrane patch, these channels could be identified as nonselective cation channels. Experiments involving substitution of the bath solution showed that the channel is impermeable for Cl and scarcely permeable for Ca2+ ions. The permeability sequence for monovalent cations, as calculated from reversal potentials, is NH4+>Na+=K+>Rb+=Li+≫TRIS+=NMDG+. Single channels are completely inhibited by flufenamic acid (50 μM), mefenamic acid (200 μM), as well as by 3′, 5-dichlorodiphenylamine-2-carboxylate. In conclusion, PGE2 activates nonselective cation channels in the basolateral membrane of cells in the base of colonic crypts. It is suggested that this mechanism initiates the secretion of K+ ions. Na+ influx through the nonselective cation channel will stimulate the Na+/K+ pump and active uptake of K+ at the basolateral side. K+ can leave the cell at the luminal side through K+-selective channels.

Key words

Nonselective cation channels Prostaglandin E2 Channel activation Colon crypt cells 

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Christiane Siemer
    • 1
  • Heinz Gögelein
    • 1
  1. 1.Max-Planck-Institut für BiophysikFrankfurt/Main 70Federal Republic of Germany
  2. 2.Department of Pharmacology, M821Hoechst AGFrankfurt/Main 80Germany

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