{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T01:14:01Z","timestamp":1769735641434,"version":"3.49.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:p>Bovine adrenocortical cells express bTREK-1 K<jats:sup>+<\/jats:sup>(bovine KCNK2) channels that are inhibited by ANG II through a Gq-coupled receptor by separate Ca<jats:sup>2+<\/jats:sup>and ATP hydrolysis-dependent signaling pathways. Whole cell and single patch clamp recording from adrenal zona fasciculata (AZF) cells were used to characterize Ca<jats:sup>2+<\/jats:sup>-dependent inhibition of bTREK-1. In whole cell recordings with pipette solutions containing 0.5 mM EGTA and no ATP, the Ca<jats:sup>2+<\/jats:sup>ionophore ionomycin (1 \u03bcM) produced a transient inhibition of bTREK-1 that reversed spontaneously within minutes. At higher concentrations, ionomycin (5\u201310 \u03bcM) produced a sustained inhibition of bTREK-1 that was reversible upon washing, even in the absence of hydrolyzable [ATP]<jats:sub>i<\/jats:sub>. BAPTA was much more effective than EGTA at suppressing bTREK-1 inhibition by ANG II. When intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was buffered to 20 nM with either 11 mM BAPTA or EGTA, ANG II (10 nM) inhibited bTREK-1 by 12.0 \u00b1 4.5% ( n=11) and 59.3 \u00b1 8.4% ( n=4), respectively. Inclusion of the water-soluble phosphatidylinositol 4,5-bisphosphate (PIP<jats:sub>2<\/jats:sub>) analog DiC<jats:sub>8<\/jats:sub>PI(4,5)P<jats:sub>2<\/jats:sub>in the pipette failed to increase bTREK-1 expression or reduce its inhibition by ANG II. The open probability ( P<jats:sub>o<\/jats:sub>) of unitary bTREK-1 channels recorded from inside-out patches was reduced by Ca<jats:sup>2+<\/jats:sup>(10\u201335 \u03bcM) in a concentration-dependent manner. These results are consistent with a model in which ANG II inhibits bTREK-1 K<jats:sup>+<\/jats:sup>channels by a Ca<jats:sup>2+<\/jats:sup>-dependent mechanism that does not require the depletion of membrane-associated PIP<jats:sub>2<\/jats:sub>. They further indicate that the Ca<jats:sup>2+<\/jats:sup>source is located in close proximity within a \u201cCa<jats:sup>2+<\/jats:sup>nanodomain\u201d of bTREK-1 channels, where [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>may reach concentrations of &gt;10 \u03bcM. bTREK-1 is the first two-pore K<jats:sup>+<\/jats:sup>channel shown to be inhibited by Ca<jats:sup>2+<\/jats:sup>through activation of a G protein-coupled receptor.<\/jats:p>","DOI":"10.1152\/ajpcell.00117.2011","type":"journal-article","created":{"date-parts":[[2011,5,26]],"date-time":"2011-05-26T03:08:06Z","timestamp":1306379286000},"page":"C619-C629","source":"Crossref","is-referenced-by-count":9,"title":["Calcium-dependent inhibition of adrenal TREK-1 channels by angiotensin II and ionomycin"],"prefix":"10.1152","volume":"301","author":[{"given":"John J.","family":"Enyeart","sequence":"first","affiliation":[{"name":"Department of Neuroscience, The Ohio State University, College of Medicine and Public Health, 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