{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:01:11Z","timestamp":1793314871627,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,7,21]],"date-time":"2007-07-21T00:00:00Z","timestamp":1184976000000},"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":[[2007,8]]},"abstract":"<jats:p>Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup>\u2010stimulated adenylyl cyclases (AC) are known to play important roles in neurons but have not previously been reported in the heart. Here we present the first evidence for selective expression of Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup>\u2010stimulated AC in the sino\u2010atrial node (SAN) but not in ventricular muscle of the guinea\u2010pig heart. The AC1 isoform of Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup>\u2010stimulated AC was shown to be present in SAN, both as mRNA using RT\u2010PCR and as protein using immuno\u2010blotting with a specific antibody. Confocal immuno\u2010fluorescence studies detected membrane localization of AC1 in SAN cells, but no AC1 in ventricular muscle. Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup>\u2010stimulated AC8 may also be present in SAN. The functional importance of AC activity was investigated by monitoring activation of <jats:italic>I<\/jats:italic><jats:sub>f<\/jats:sub> (gated by hyperpolarization and regulated by cAMP, which shifts activation to more depolarized voltages). Basal activity of AC in isolated SAN myocytes was demonstrated by the observations that an inhibitor of AC activity (MDL 12330A, 10 \u03bc<jats:sc>m<\/jats:sc>) shifted activation in the hyperpolarizing direction, while inhibition of phosphodiesterases (IBMX, 100 \u03bc<jats:sc>m<\/jats:sc>) shifted <jats:italic>I<\/jats:italic><jats:sub>f<\/jats:sub> activation in the depolarizing direction. Buffering cytosolic Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup> with the Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup> chelator BAPTA (by exposure to BAPTA\u2010AM) shifted activation of <jats:italic>I<\/jats:italic><jats:sub>f<\/jats:sub> in the hyperpolarizing direction, and under these conditions the AC inhibitor MDL had little or no further effect. The actions of BAPTA were overcome by exposure to forskolin (10 \u03bc<jats:sc>m<\/jats:sc>), a direct stimulator of all AC isoforms, to restore cAMP levels. These effects are consistent with the functional importance of Ca<jats:sup>2<\/jats:sup><jats:sup><jats:bold>+<\/jats:bold><\/jats:sup>\u2010stimulated AC, which is expected to be fundamental to initiation and regulation of the heartbeat.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.133439","type":"journal-article","created":{"date-parts":[[2007,6,1]],"date-time":"2007-06-01T00:24:31Z","timestamp":1180657471000},"page":"1195-1203","source":"Crossref","is-referenced-by-count":125,"title":["Ca<sup>2+<\/sup>\u2010stimulated adenylyl cyclase isoform AC1 is preferentially expressed in guinea\u2010pig sino\u2010atrial node cells and modulates the <i>I<\/i><sub>f<\/sub> pacemaker current"],"prefix":"10.1113","volume":"582","author":[{"given":"Paul","family":"Mattick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Parrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efe","family":"Odia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Terrar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,7,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/72072"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00677.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.66.3.633"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/351145a0"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017343"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1988.sp017344"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.21.12438"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017488"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00580674"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.18.8774"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374956"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.20.9809"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00153-X"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00668-5"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.100305"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00357a021"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000204575.94040.d1"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/35081088"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.3.463"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)80036-2"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.15.6716"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.677ba.x"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2007.133439","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2007.133439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T01:56:03Z","timestamp":1696989363000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2007.133439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7,21]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1113\/jphysiol.2007.133439"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2007.133439","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,7,21]]}}}