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Hypotonic stress activates an intermediate conductance K+ channel in human colonic crypt cells

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Abstract Aim: 

To investigate the effect of hypotonic stress on human colonic crypts cells in terms of ion channel activity and intracellular Ca2+ concentration. Methods: 

Single crypts were isolated from biopsies taken during colonoscopy. The patch clamp technique was used (in the cell-attached mode) to observe the activity of ion channels during hypotonic stress. Calcium measurements were made using the fluophores Fluo 3 or 4. Results: 

The intermediate conductance (29 pS), Ca2+-sensitive, K+ channel (also known as KCNN4) previously described ( Sandle et al. 1994 ) was seen in 54 of 149 patches (36%) when the crypts were bathed in normal extracellular solution (290 mOsm kg−1). Forty-one patches could be used for further analysis. Activation of one or several 29 pS channels was seen in 15 of 41 patches (39%) after 30 s to 4 min of exposure to hypotonic solution (160 mOsm kg−1). The open probability increased from 0.0043 in control solution to 0.44 at 5 min of hypotonic stress. When the crypts were exposed to hypotonic solution, an increase in intracellular Ca2+ could be seen. The increase in intracellular Ca2+ emanates mainly from intracellular stores. Conclusion: 

The 29 pS K+ channel takes part in volume regulation in human colonic crypt cells. The activation of this channel is mediated through an increase in intracellular Ca2+.

Keywords: KCNN4; crypt cells; human colon; hypotonic stress; intracellular Ca2+; potassium channel

Document Type: Research Article


Affiliations: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Publication date: December 1, 2004

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