Activation of chloride channels in the mpkCCD cl4 renal cell line in response to lysophosphatic acid (LPA)

The mpkCCD cl4 (mouse principal cells of the kidney cortical collecting duct, clone 4) cell line is a well characterized model of the principal cells of the distal nephron/collecting duct (Benz et al., JASN 10:923, 1999). This cell type responds to hormones responsible for salt and fluid homeostasis. Electrophysiological techniques have been widely used to study hormonally stimulated ion transport but the effects of other stimuli, particularly those involved in renal injury and/or inflammatory responses is less well characterized. We have found that basolateral addition of LPA or fetal bovine serum (10% v/v) to mpkCCD cl4 cells elicits a characteristic Cl − secretory response that involves both CFTR (cystic fibrosis transmembrane conductance regulator) and the recently described Ca 2+ ‐activated Cl − channel, TMEM16a. Both serum and LPA are components released into the interstitial space during renal injury and LPA is released during inflammatory responses. Serum contains sufficient LPA to maximally stimulate Cl − secretory pathways. Under normal conditions, the LPA is bound to serum proteins such as albumin and gelsolin and is, therefore, sequestered from the basolateral receptors on epithelial cells. The stimulation of epithelial ion transport may play an important role in the response to injury/inflammation. Funding: IUPUI Membrane Biosciences Signature Center Grant