{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:22:33Z","timestamp":1781108553536,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1991,8,15]]},"abstract":"<jats:p>The cAMP-dependent regulation of ion channels was studied by using the whole-cell configuration of the patch clamp technique. In isolated cardiac ventricular myocytes, the beta-adrenergically regulated Cl- current (ICl) exhibited an unusual dependence on Na+, such that replacement of extracellular Na+ with compounds such as tetramethylammonium, choline, Tris, or N-methyl-D-glucamine resulted in a reduction in current amplitude without changing the reversal potential. Replacement of extracellular Na+ with tetramethylammonium also reduced the magnitude of the beta-adrenergically enhanced Ca2+ current and delayed rectifier K+ current, suggesting that removal of Na+ was affecting the cAMP pathway that regulates all three currents. Replacement of extracellular Na+ also reduced ICl that was stimulated by (i) direct activation of adenylate cyclase with forskolin, (ii) inhibition of phosphodiesterase with 3-isobutyl-1-methylxanthine, (iii) exposure to the membrane-permeable cAMP derivative 8-bromoadenosine 3',5'-cyclic monophosphate, or (iv) direct phosphorylation of the channel with protein kinase A catalytic subunit. This suggests that the Na+ dependence is at a point beyond the activation of protein kinase A. The Na+ dependence of ICl regulation could not be explained by changes in intracellular Ca2+. However, the sensitivity of the ICl to changes in extracellular Na+ depended significantly on the intracellular Na+ concentration, suggesting that intracellular Na+ plays an important role in the cAMP-dependent regulation of ion channels.<\/jats:p>","DOI":"10.1073\/pnas.88.16.6946","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:43:48Z","timestamp":1149061428000},"page":"6946-6950","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Intracellular Na+ modulates the cAMP-dependent regulation of ion channels in the heart."],"prefix":"10.1073","volume":"88","author":[{"given":"R D","family":"Harvey","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Nevada School of Medicine, Reno 89557."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Jurevicius","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Nevada School of Medicine, Reno 89557."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R","family":"Hume","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Nevada School of Medicine, Reno 89557."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1991,8,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.88.16.6946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:02:36Z","timestamp":1649854956000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.88.16.6946"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,8,15]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1991,8,15]]}},"alternative-id":["10.1073\/pnas.88.16.6946"],"URL":"https:\/\/doi.org\/10.1073\/pnas.88.16.6946","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,8,15]]},"assertion":[{"value":"1991-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}