{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:14:06Z","timestamp":1771632846513,"version":"3.50.1"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,6,1]]},"abstract":"<jats:p>The mechanism of G protein beta gamma subunit (G beta gamma)-induced activation of the muscarinic K+ channel (KACh) in the guinea pig atrial cell membrane was examined using the inside-out patch clamp technique. G beta gamma and GTP-gamma S-bound alpha subunits (G alpha *'s) of pertussis toxin (PT)-sensitive G proteins were purified from bovine brain. Either in the presence or absence of Mg2+, G beta gamma activated the KACh channel in a concentration-dependent fashion. 10 nM G beta gamma almost fully activated the channel in 132 of 134 patches (98.5%). The G beta gamma-induced maximal channel activity was equivalent to or sometimes larger than the GTP-gamma S-induced one. Half-maximal activation occurred at approximately 6 nM G beta gamma. Detergent (CHAPS) and boiled G beta gamma preparation could not activate the KACh channel. G beta gamma suspended by Lubrol PX instead of CHAPS also activated the channel. Even when G beta gamma was pretreated in Mg(2+)-free EDTA internal solution containing GDP analogues (24-48 h) to inactivate possibly contaminating G i alpha *'s, the G beta gamma activated the channel. Furthermore, G beta gamma preincubated with excessive GDP-bound G o alpha did not activate the channel. These results indicate that G beta gamma itself, but neither the detergent CHAPS nor contaminating G i alpha *, activates the KACh channel. Three different kinds of G i alpha * at 10 pM-10 nM could weakly activate the KACh channel. However, they were effective only in 40 of 124 patches (32.2%) and their maximal channel activation was approximately 20% of that induced by GTP-gamma S or G beta gamma. Thus, G i alpha * activation of the KACh channel may not be significant. On the other hand, G i alpha *'s effectively activated the ATP-sensitive K+ channel (KATP) in the ventricular cell membrane when the KATP channel was maintained phosphorylated by the internal solution containing 100 microM Mg.ATP. G beta gamma inhibited adenosine or mACh receptor-mediated, intracellular GTP-induced activation of the KATP channel. G i alpha *'s also activated the phosphorylated KATP channel in the atrial cell membrane, but did not affect the background KACh channel. G beta gamma subsequently applied to the same patch caused prominent KACh channel activation. The above results may indicate two distinct regulatory systems of cardiac K+ channels by PT-sensitive G proteins: G i alpha activation of the KATP channel and G beta gamma activation of the KACh channel.<\/jats:p>","DOI":"10.1085\/jgp.99.6.961","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:48:59Z","timestamp":1084492139000},"page":"961-983","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":152,"title":["On the mechanism of G protein beta gamma subunit activation of the muscarinic K+ channel in guinea pig atrial cell membrane. Comparison with the ATP-sensitive K+ channel."],"prefix":"10.1085","volume":"99","author":[{"given":"H","family":"Ito","sequence":"first","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R T","family":"Tung","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Takahashi","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Katada","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Ui","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Kurachi","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1992,6,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/99\/6\/961\/1814837\/961.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/99\/6\/961\/1814837\/961.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T12:38:24Z","timestamp":1690461504000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/99\/6\/961\/28066\/On-the-mechanism-of-G-protein-beta-gamma-subunit"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,6,1]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[1992,6,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.99.6.961","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,6,1]]}}}