{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T10:05:28Z","timestamp":1760954728851},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3778,"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":[[1998,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The sinus node inhibitors UL\u2013FS 49 and DK\u2013AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino\u2010atrial (SA) node, which might originate from the use\u2010dependent blockade of a hyperpolarization\u2010activated current I<jats:sub>f<\/jats:sub>. A hyperpolarization\u2010activated current I<jats:sub>h<\/jats:sub>, which is present in many types of neurons, is similar to I<jats:sub>f<\/jats:sub>. We studied the effects of these drugs on I<jats:sub>h<\/jats:sub> in cultured mouse dorsal root ganglion (DRG) neurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>With the whole\u2010cell patch\u2010clamp technique use\u2010dependent block of I<jats:sub>h<\/jats:sub> was observed. The steady\u2010state block following a voltage\u2010clamp pulse train (1\u2010s steps from \u221238 to \u2212108\u2003mV applied at 0.5\u2003Hz) was dependent on drug concentration and showed an apparent K<jats:sub>d<\/jats:sub> of 0.1 and 0.79\u2003\u03bc<jats:sc>M<\/jats:sc> with DK\u2013AH 269 and UL\u2013FS 49 respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The rate of block increased linearly with drug concentration. The rate of recovery from block was, however, much slower compared to cardiac tissue.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>There was no significant effect of UL\u2013FS 49 on the activation curve.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At high concentrations of UL\u2013FS 49 a clear association of the drug with the open channel was observed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When the cell was stimulated at a frequency of 3\u2003Hz, a distinct hyperpolarization was observed in the presence of extracellular Cs<jats:sup>+<\/jats:sup> or when I<jats:sub>h<\/jats:sub> was blocked with UL\u2013FS 49, but not in the absence of Cs<jats:sup>+<\/jats:sup> and UL\u2013FS 49.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results indicate that I<jats:sub>h<\/jats:sub> protects the cell against hyperpolarizations and subsequent inexcitability. The action of the drugs on the hyperpolarization\u2010activated current in cardiac and neuronal tissue show some similarities; however, some pronounced differences indicate that different subtypes of the channel might exist.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>125<\/jats:bold>, 741\u2013750; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702153\">10.1038\/sj.bjp.0702153<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702153","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:50:22Z","timestamp":1106941822000},"page":"741-750","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Use\u2010dependent block of I<sub>h<\/sub> in mouse dorsal root ganglion neurons by sinus node inhibitors"],"prefix":"10.1111","volume":"125","author":[{"given":"A","family":"Raes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Van de Vijver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Goethals","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P P","family":"van Bogaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/1911104a0"},{"key":"e_1_2_5_3_1","volume-title":"Sinus node inhibitors. 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