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Aldosterone activates colonic K secretion via BK channels (KCa1.1) and membrane trafficking (1097.9)
Author(s) -
Halm Susan,
Halm Dan
Publication year - 2014
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.28.1_supplement.1097.9
Subject(s) - aldosterone , apical membrane , microbiology and biotechnology , chemistry , clathrin , endocytosis , medicine , endocrinology , biology , receptor , biochemistry , membrane
Aldosterone (aldo) activates electrogenic K + secretion in guinea pig distal colon via a mechanism requiring protein synthesis. Channel blocker sensitivity supported conductive apical K + exit and basolateral Cl ‐ exit during aldo stimulation, similar to adrenergic activation. Paxilline [1 μM], BK channel (K Ca 1.1, Kcnma1 ) blocker, inhibited ~50% of short‐circuit current (I sc ) and transepithelial conductance (G t ) activated by aldo; and, CaCCinh‐A01 [30 μM], Ca ++ ‐activated Cl ‐ channel blocker, eliminated aldo I sc and decreased aldo G t . Signaling for K + secretion by aldo involved cAMP and serum‐glucocorticoid protein kinase (sgk) as indicated by elimination of aldo I sc with inhibition of soluble adenylyl cyclase by KH7 [30 μM] or sgk by GSK‐650394 [10 μM]. Elimination of aldo I sc by inhibiting dynamin (dyngo‐4a [30 μM]) or clathrin (pitstop‐2 [20 μM]) indicated a requirement for clathrin dependent endocytosis during aldo signaling. Manipulating the ubiquitylation cycle by inhibiting ubiquitin‐E1 ligase (UBEI‐41 [50 μM]) also inhibited aldo I sc ; and, disrupting membrane localization of small GTPases such as ras, rho, or rab with farnesyltiosalicylate [10 μM] abolished aldo I sc . Dependence on microtubular transport was supported by loss of aldo I sc with inhibiting dynein (ciliobrevin‐D [10 μM]). Together these results support an aldosterone signaling mechanism for activating electrogenic K + secretion involving cAMP, sgk, endocytosis, and microtubular transport. [NIH DK65845]