{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:57:49Z","timestamp":1791215869224,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2346,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2002,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Regulation of the slowly activating component of delayed rectifier K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>) by intracellular guanosine 3\u20325\u2032 cyclic monophosphate (cGMP) was investigated in guinea\u2010pig sino\u2010atrial (SA) node cells using the whole\u2010cell patch\u2010clamp method.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When a cell was dialyzed with pipette solution containing 100 \u03bc<jats:sc>M<\/jats:sc> cGMP, <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> started to gradually increase and reached a maximum increase of a factor of 2.37\u00b10.39 (<jats:italic>n<\/jats:italic>=4) about 10\u201315 min after rupture of patch membrane. Atrial natriuretic peptide (ANP, 100 n<jats:sc>M<\/jats:sc>) also potentiated <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>, consistent with intracellular cGMP\u2010induced enhancement of <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Bath application of a selective blocker of the cGMP\u2010inhibited phosphodiesterase (PDE3) milrinone (100 \u03bc<jats:sc>M<\/jats:sc>) enhanced <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> by a factor of 1.50\u00b10.09 (<jats:italic>n<\/jats:italic>=4) but failed to further enhance <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> after a maximum stimulation by intracellular cGMP (100 \u03bc<jats:sc>M<\/jats:sc>), suggesting that blockade of PDE3 activity is involved in the enhancement of <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>. A potent but nonspecific PDE inhibitor 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX, 100 \u03bc<jats:sc>M<\/jats:sc>) further increased <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> stimulated by 100 \u03bc<jats:sc>M<\/jats:sc> milrinone, indicating that PDE subtypes other than PDE3 are also involved in the regulation of basal <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> in guinea\u2010pig SA node cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Bath application of 100 \u03bc<jats:sc>M<\/jats:sc> 8\u2010bromoguanosine 3\u20325\u2032 cyclic monophosphate (8\u2010Br\u2010cGMP) increased <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> by a factor of 1.48\u00b10.11 (<jats:italic>n<\/jats:italic>=5) and this stimulatory effect was totally abolished by cGMP\u2010dependent protein kinase (PKG) inhibitor KT\u20105823 (500 n<jats:sc>M<\/jats:sc>), suggesting that the activation of PKG also mediates cGMP\u2010induced potentiation of <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results strongly suggest that intracellular cGMP potentiates <jats:italic>I<\/jats:italic><jats:sub>Ks<\/jats:sub> not only by blocking PDE3 but also by activating PKG in guinea\u2010pig SA node cells.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>137<\/jats:bold>, 127\u2013137. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704843\">10.1038\/sj.bjp.0704843<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704843","type":"journal-article","created":{"date-parts":[[2002,9,18]],"date-time":"2002-09-18T00:15:48Z","timestamp":1032308148000},"page":"127-137","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Potentiation of slow component of delayed rectifier K<sup>+<\/sup> currentby cGMP <i>via<\/i> two distinct mechanisms: inhibition of phosphodiesterase 3 and activation of protein kinase G"],"prefix":"10.1111","volume":"137","author":[{"given":"Kentaro","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Shintani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Guang","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Matsuura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Bamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"H921","article-title":"Delayed rectification in single cells isolated from guinea pig sinoatrial node","volume":"262","author":"ANUMONWO J.M.B.","year":"1992","journal-title":"Am. 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