Short-chain fatty acid (SCFA) volume regulation in proximal and distal rabbit colon is different

SCFAs increase the volume of many different cell types rarely exposed to significant concentrations of these weak electrolytes. SCFAs swell isolated cells from colonic carcinoma cell lines, but the-mechanism(s) of volume regulation in normal colonocytes, which are generally exposed to > 100 mM SCFAs, has not been well characterized. AIMS. To determine the effect of SCFAs on volume regulation in proximal and distal rabbit colonocytes. METHODS. Isolated colonocytes were plated on coverslips and placed in a perfusion apparatus that permitted fluid changes. Cells were continuously monitored by video-microscopy; volume was estimated by measured changes in the radius of individual cells. RESULTS. Distal colonocytes (DC) consistently had a slightly greater basal volume than proximal colonocytes (PC): [14.2 pl/fl:9.8 pl/fl] In HEPES-buffered solutions, an isotonic change to a 90 mM NaCl/50 mM Na propionate solution elicited a significant increase in cell volume within 10 min, but no noticeable regulatory volume decrease over 30 min: V/Vo in DC: 1.29 +/- .09; in PC: 1.25 +/- .05. In HCO3-buffered solutions, 50 mM PROP caused significantly greater cell swelling; in DC: 1.74 +/- .21; in PC: 1.52 +/- .08. In DC both amiloride and EIPA blocked the SCFA-induced increase in cell volume. A hypotonic challenge confirmed that these cells were capable of swelling. In contrast, amiloride did not significantly inhibit SCFA-induced swelling in PC: control, 1.25 +/- .05; amiloride, 1.36 +/- .10. Cell volume increased in PC perfused with an isosmotic 50 mM propionate, Na-free solution: 1.22 +/- .04. CONCLUSIONS. (i) SCFAs induce significant cell swelling, but no regulatory volume decrease, in isolated colonocytes; (ii) HCO3 augments SCFA-induced cell swelling; (iii) volume increase in DC is dependent on Na-H exchange, but in PC appears to be Na-independent. SIGNIFICANCE. There are fundamental differences in how proximal and distal colon respond to isosmotic volume challenge of SCFAs.