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SK4 mediated K + secretion depends on P2Y receptor localization in human mammary epithelial cells
Author(s) -
Schiller Katherine R.,
O’Grady Scott M.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1201.11
Subject(s) - apical membrane , charybdotoxin , chemistry , epithelial polarity , stimulation , bk channel , receptor , secretion , potassium channel , medicine , iberiotoxin , endocrinology , biophysics , microbiology and biotechnology , membrane potential , biochemistry , biology , membrane
Immortalized human mammary epithelial cells express multiple P2Y receptors that are localized in both apical and basolateral membranes. Basolateral UTP (10 μM) stimulation of monolayers mounted in Ussing chambers produced an increase in ENaC‐dependent Na + absorption resulting in part from SK4 channel activation in the basolateral membrane. In contrast apical stimulation with UTP (10 μM) produced a transient decrease in Isc consistent with transepithelial K + secretion. Inhibition of Ca 2+ mobilization evoked by UTP using BAPTA‐AM abolished the decrease in Isc. In addition, pretreatment with a known Ca 2+ ‐activated K + channel toxin, charybdotoxin (200 nM), blocked the Isc response by >70%. A similar degree of inhibition was produced by pretreatment with clotrimazole (10 μM) and TRAM‐34 (0.5 μM). Apical addition of the selective BK channel inhibitor, iberiotoxin also affected the response to apical UTP by stimulating oscillations in the Isc. These results suggest that apical UTP stimulation elicits K + secretion that is mediated by BK and SK4 potassium channels. Moreover, apical UTP failed to stimulate ENaC‐dependent Na + absorption observed following basolateral UTP treatment, suggesting that the Ca 2+ ‐mobilizing effects of apical UTP are limited to the apical membrane.