Colonic epithelial ion transport is not affected in patients with diverticulosis

Abstract

Background: Colonic diverticular disease is a bothersome condition with an unresolved pathogenesis. It is unknown whether a neuroepithelial dysfunction is present. The aim of the study was two-fold; (1) to investigate colonic epithelial ion transport in patients with diverticulosis and (2) to adapt a miniaturized Modified Ussing Air-Suction (MUAS) chamber for colonic endoscopic biopsies.

Methods: Biopsies were obtained from the sigmoid part of the colon. 86 patients were included. All patients were referred for colonoscopy on suspicion of neoplasia and they were without pathological findings at colonoscopy (controls) except for diverticulosis in 22 (D-patients). Biopsies were mounted in MUAS chambers with an exposed area of 5 mm2. Electrical responses to various stimulators and inhibitors of ion transport were investigated together with histological examination. The MUAS chamber was easy to use and reproducible data were obtained.

Results: Median basal short circuit current (SCC) was 43.8 microA x cm(-2) (0.8 - 199) for controls and 59.3 microA x cm(-2) (3.0 - 177.2) for D-patients. Slope conductance was 77.0 mS x cm(-2) (18.6 - 204.0) equal to 13 Omega x cm(2) for controls and 96.6 mS x cm(-2) (8.4 - 191.4) equal to 10.3 Omega x cm(2) for D-patients. Stimulation with serotonin, theophylline, forskolin and carbachol induced increases in SCC in a range of 4.9 - 18.6 microA x cm(-2), while inhibition with indomethacin, bumetanide, ouabain and amiloride decreased SCC in a range of 6.5 - 27.4 microA x cm(-2), and all with no significant differences between controls and D-patients. Histological examinations showed intact epithelium and lamina propria before and after mounting for both types of patients.

Conclusion: We conclude that epithelial ion transport is not significantly altered in patients with diverticulosis and that the MUAS chamber can be adapted for studies of human colonic endoscopic biopsies.

Figure 1

Trace showing the change in SCC following application of carbachol, 10 μM (N = 6, n = 18). Arrow marks the time of adding the compoud.

Figure 2

Trace showing the change in SCC following application of 5-HT, 100 μM (N = 21, n = 29). Arrow marks the time of adding the compoud.

Figure 3

Trace showing the change in SCC following application of theophylline 100 μM (N = 31, n = 39). Arrow marks the time of adding the compoud.

Figure 4

Trace showing the change in SCC following application of forskolin, 1 μM (N = 23, n = 32). Arrow marks the time of adding the compoud.

Figure 5

Trace showing the change in SCC following application of amiloride, 100 μM (N = 20, n = 43). Arrow marks the time of adding the compoud.

Figure 6

Trace showing the change in SCC following application of bumetanide, 2.5 μM (N = 16, n = 26). Arrow marks the time of adding the compoud.

Figure 7

Trace showing the change in SCC following application of indometacin, 40 μM (N = 17, n = 27). Arrow marks the time of adding the compoud.

Figure 8

Trace showing the change in SCC following application of ouabain, 200 nM (N = 28, n = 43). Arrow marks the time of adding the compoud.

Figure 9

Micrographs of hematoxylin/periodic acid Schiff stained colonic biopsies. (A) biopsy from control patient – not mounted. (B) biopsy from control patient – mounted for 2 hrs in the MUAS chamber. The histology is the same and in particular the epithelial surface is intact. Similar results exist for biopsies from D-patients, not shown.