{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:04:24Z","timestamp":1762430664153},"reference-count":42,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"Na\/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na+<\/jats:sup>and energy metabolism in regulating Na\/K pump activity and neuronal excitability. Removal of extracellular K+<\/jats:sup>to block the Na\/K pump excited SCN neurons to fire at higher rates and return to normal K+<\/jats:sup>to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K+<\/jats:sup>-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na+<\/jats:sup>imaging with a Na+<\/jats:sup>-sensitive fluorescent dye indicated saturating accumulation of intracellular Na+<\/jats:sup>in response to pump blockade with zero K+<\/jats:sup>. The Na+<\/jats:sup>ionophore monensin also induced Na+<\/jats:sup>loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na+<\/jats:sup>or by pump blockade. Conversely, Na+<\/jats:sup>depletion with Na+<\/jats:sup>-free pipette solution depolarized membrane potential but retained residual Na\/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na\/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na+<\/jats:sup>levels in all cells. Nonetheless, the Na\/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na\/K pump. Together, the results indicate the importance of intracellular Na+<\/jats:sup>and energy metabolism in regulating Na\/K pump activity as well as neuronal excitability in the SCN neurons.<\/jats:p>","DOI":"10.1152\/jn.00361.2012","type":"journal-article","created":{"date-parts":[[2012,7,6]],"date-time":"2012-07-06T06:41:29Z","timestamp":1341556889000},"page":"2024-2032","source":"Crossref","is-referenced-by-count":25,"title":["Intracellular Na+<\/sup>and metabolic modulation of Na\/K pump and excitability in the rat suprachiasmatic nucleus neurons"],"prefix":"10.1152","volume":"108","author":[{"given":"Yi-Chi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyh-Jeen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Chi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(00)00038-2"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.3.763"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00360-010-0451-4"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.166918"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00939.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021909-135821"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0576-1"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.4.1791"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.08.022"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90361-4"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(82)90189-6"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05581.x"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1987.253.1.F26"},{"key":"B14","doi-asserted-by":"crossref","first-page":"19458","DOI":"10.1016\/S0021-9258(19)47322-5","volume":"264","author":"Harootunian AT","year":"1989","journal-title":"J Biol Chem"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200910270"},{"volume-title":"2010 Abstract Viewer\/Itinerary Planner","year":"2010","author":"Hsu YT","key":"B16"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00164-8"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.11.5962"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1840-07.2007"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2146-04.2004"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.03950.x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605757103"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00736-1"},{"key":"B24","doi-asserted-by":"crossref","first-page":"19449","DOI":"10.1016\/S0021-9258(19)47321-3","volume":"264","author":"Minta A","year":"1989","journal-title":"J Biol Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.94.3.539"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(92)07008-C"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.12-06-02015.1992"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.22.040182.002341"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.69.5.605"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1971.tb00013.x"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1126\/science.887940"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00343.x"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)91041-1"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1998.275.5.H1808"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2010.06.006"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.279.3.C541"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00061.2004"},{"volume-title":"2006 Abstract Viewer\/Itinerary Planner","year":"2006","author":"Wang YC","key":"B38"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01369.2005"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(89)90165-3"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91978-X"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308709101"}],"container-title":["Journal of Neurophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/jn.00361.2012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T11:11:10Z","timestamp":1642677070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/jn.00361.2012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,1]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2012,10,1]]}},"alternative-id":["10.1152\/jn.00361.2012"],"URL":"https:\/\/doi.org\/10.1152\/jn.00361.2012","relation":{},"ISSN":["0022-3077","1522-1598"],"issn-type":[{"type":"print","value":"0022-3077"},{"type":"electronic","value":"1522-1598"}],"subject":[],"published":{"date-parts":[[2012,10,1]]}}}