{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:05:23Z","timestamp":1790755523581,"version":"4.1.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1997,1,1]]},"abstract":"<jats:p>Jiang, Chun and Gabriel G. Haddad. Modulation of K<jats:sup>+<\/jats:sup>channels by intracellular ATP in human neocortical neurons. J. Neurophysiol. 77: 93\u2013102, 1997. ATP-modulated K<jats:sup>+<\/jats:sup>channels play an important role in regulating membrane excitability during metabolic stress. To characterize such K<jats:sup>+<\/jats:sup>channels from the human brain, single channel currents were studied in excised inside-out patches from freshly dissociated human neocortical neurons. Three currents that were sensitive to physiological concentrations of ATP and selectively permeable to K<jats:sup>+<\/jats:sup>were identified. One of these currents had a unitary conductance of \u223c47 pS and showed a strong inward rectification with symmetric K<jats:sup>+<\/jats:sup>concentrations across the membrane. This K<jats:sup>+<\/jats:sup>current was inhibited by ATP in a concentration-dependent manner with an IC<jats:sub>50<\/jats:sub>(half-inhibition of channel activity) of \u223c130 \u03bcM. Channel activity also was suppressed by ADP, nonhydrolyzable ATP analogue AMP-PNP, and sulfonylurea receptor\/channel blocker glibenclamide. The second K<jats:sup>+<\/jats:sup>current had a unitary conductance of \u223c200 pS and showed a weak inward rectification. Similarly, this current was inhibited by ATP (IC<jats:sub>50<\/jats:sub>= 350 \u03bcM), AMP-PNP, and glibenclamide. Unlike the small-conductance ATP-inhibitable K<jats:sup>+<\/jats:sup>channel (S-K<jats:sub>ATP<\/jats:sub>), activation of this large-conductance K<jats:sup>+<\/jats:sup>channel (L-K<jats:sub>ATP<\/jats:sub>) required the presence of micromolar concentration of Ca<jats:sup>2+<\/jats:sup>in the internal solution, but charybdotoxin did not inhibit this channel. The third K<jats:sup>+<\/jats:sup>current was also Ca<jats:sup>2+<\/jats:sup>dependent and had a large conductance (\u223c280 pS). It was inhibited by external charybdotoxin, iberiotoxin, and tetraethylammonium. In contrast to the other two K<jats:sub>ATP<\/jats:sub>channels, ATP enhanced channel open-state probability and unitary conductance, and glibenclamide at concentration of 10\u201320 \u03bcM had no inhibitory effect on this current. K<jats:sup>+<\/jats:sup>channels that have single-channel and pharmacological properties similar to these three human ATP-modulated K<jats:sup>+<\/jats:sup>channels also were observed in experiments on rat neocortical neurons. These results therefore indicate that K<jats:sub>ATP<\/jats:sub>channels are expressed in human neocortical neurons, and two distinct K<jats:sub>ATP<\/jats:sub>channels (S-K<jats:sub>ATP<\/jats:sub>and L-K<jats:sub>ATP<\/jats:sub>) exist in the human and rat neurons. The observation that ATP at different concentrations modulates different K<jats:sup>+<\/jats:sup>channels suggests that metabolic rate may be continuously sensed in neurons with resulting alterations in neuronal membrane excitability.<\/jats:p>","DOI":"10.1152\/jn.1997.77.1.93","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T01:09:16Z","timestamp":1514164156000},"page":"93-102","source":"Crossref","is-referenced-by-count":51,"title":["Modulation of K<sup>+<\/sup>Channels by Intracellular ATP in Human Neocortical Neurons"],"prefix":"10.1152","volume":"77","author":[{"given":"Chun","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Respiratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, and"},{"name":"Department of Biology, Georgia State University, Atlanta, Georgia 30322-4010"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel G.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Respiratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.11.030188.000525"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/312446a0"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373626"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14116.x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/BF00582512"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1993.264.5.C1190"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1857986"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/311271a0"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116241"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp018939"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(88)90561-5"},{"key":"B13","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/S0022-3565(25)24756-5","volume":"257","author":"Gopalakrishnan M.","year":"1991","journal-title":"J. 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