{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:32:15Z","timestamp":1777462335946,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T00:00:00Z","timestamp":1152144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,7,15]]},"abstract":"<jats:p>Some studies report that the positive relationship between L\u2010type Ca<jats:sup>2+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub>) and frequency in cardiac myocytes is mainly due to a direct negative feedback of sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> release on <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> inactivation while others provide evidence for activation of calmodulin kinase II (CaMKII). To further elucidate the role of endogenous CaMKII activity, the CaMKII inhibitory peptides, autocamtide\u20102 relating inhibitory peptide (AIP) and myristoylated AIP were applied using conventional and perforated patch\u2010clamp methods. AIP inhibited the normal adaptive increase in <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> in response to abrupt increase in pacing frequency from 0.05 to 2 Hz. The positive <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub>\u2013frequency relationship was reversed by AIP and the inhibitory effect of AIP was significantly exaggerated at fast pacing rates. The onset of inactivation of <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> was not altered by AIP. After thapsigargin treatment, AIP slowed recovery from inactivation of <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> and this effect was exaggerated during fast pacing. Buffering of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> by BAPTA and EGTA accelerated recovery of <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> from inactivation, and BAPTA partly eliminated the effect of AIP on the recovery. We conclude that: (1) [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> directly slows <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> recovery from inactivation; and (2) Ca<jats:sup>2+<\/jats:sup>\u2010dependent endogenous CaMKII activity accelerates the <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> recovery. Thus, at fast heart rates, elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> activates endogenous CaMKII and compensates for its direct inhibitory effect on <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub> recovery from inactivation. Dynamic activity of endogenous CaMKII enhances the positive <jats:italic>I<\/jats:italic><jats:sub>Ca\u2212L<\/jats:sub>\u2013frequency relationship.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.109199","type":"journal-article","created":{"date-parts":[[2006,4,21]],"date-time":"2006-04-21T00:36:39Z","timestamp":1145579799000},"page":"509-518","source":"Crossref","is-referenced-by-count":32,"title":["Calmodulin kinase II accelerates L\u2010type Ca<sup>2+<\/sup> current recovery from inactivation and compensates for the direct inhibitory effect of [Ca<sup>2+<\/sup>]<sub>i<\/sub> in rat ventricular myocytes"],"prefix":"10.1113","volume":"574","author":[{"given":"Jiqing","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry J.","family":"Duff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.262372999"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2004.02.005"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-010-0658-3"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61108-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5348.227"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1999.1023"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35004052"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.021881"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00008086"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90053-7"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00797.x"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200505155"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2040"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511971200"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.02.025"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000069685.20258.F1"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-18-06961.1997"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.1996.0403"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80709-6"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104959200"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0387c.xd"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.062539"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00552a018"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.9.760"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.t01-1-00679.x"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.276.6.H2168"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9659"},{"key":"e_1_2_5_29_1","first-page":"H982","article-title":"Ca\u2010dependent facilitation of cardiac Ca current is due to Ca\u2010calmodulin\u2010dependent protein kinase","volume":"267","author":"Yuan W","year":"1994","journal-title":"Am J Physiol"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/20200"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002986200"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2006.109199","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2006.109199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T22:36:27Z","timestamp":1697063787000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2006.109199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,7,6]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,7,15]]}},"alternative-id":["10.1113\/jphysiol.2006.109199"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2006.109199","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,7,6]]}}}