{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T22:59:35Z","timestamp":1780527575119,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3500,"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":[[1999,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We investigated the action of the phenylalkylamines verapamil and N\u2010methyl\u2010verapamil on the Kv1.3 potassium channel using the whole\u2010cell configuration of the patch\u2010clamp technique. Our goal was to identify their binding as a prerequisite for using the phenylalkylamines as small, well\u2010defined molecular probes, not only to expand the structural findings made with peptide toxins or by crystallization, but also to use them as lead compounds for the generation of more potent and therefore more specific K<jats:sup>+<\/jats:sup> channel modulators.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Competition experiments with charybdotoxin, known to interact with external residues of Kv1.3, showed no interaction with verapamil. The internal application of quarternary N\u2010methyl\u2010verapamil in combination with verapamil suggested competition for the same internal binding site.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Verapamil affinity was decreased 6 fold by a mutation (M395V) in a region of the internal pore which forms part of the internal tetraethylammonium (TEA<jats:sup>+<\/jats:sup>) binding site, although mutations at neighbouring residues (T396 and T397) were without effect.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Modification of C\u2010type inactivation by mutations in the internal pore suggest that this region participates in the inactivation process.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The action of phenylalkylamines and local anaesthetics on L\u2010type Ca<jats:sup>2+<\/jats:sup> channels and Na<jats:sup>+<\/jats:sup> channels, respectively, and verapamil on Kv1.3 indicate very similar blocking mechanisms. This might allow the use of these compounds as molecular probes to map the internal vestibule of all three channel types.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 1065\u20131074; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702599\">10.1038\/sj.bjp.0702599<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702599","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:16:44Z","timestamp":1106943404000},"page":"1065-1074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The effect of deep pore mutations on the action of phenylalkylamines on the Kv1.3 potassium channel"],"prefix":"10.1111","volume":"127","author":[{"given":"Heiko","family":"Rauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Grissmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90104-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015548"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1992.11.163"},{"key":"e_1_2_7_5_1","first-page":"624","article-title":"Structure of \u03b1\u2010Isopropyl\u2010\u03b1\u2010[(N\u2010methyl\u2010N\u2010homoveratryl)\u2003\u2010\u03b3\u2010aminopropyl]\u20103,4\u2010dimethoxyphenylacetonitrile hydrochloride, *Verapamil, C27H38N2O4\u00b7HCL","volume":"41","author":"CARPY A.","year":"1985","journal-title":"Acta Cryst."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(92)90079-L"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.369"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-5765(05)80007-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5092"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90340-W"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.106.4.745"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/307465a0"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(85)90035-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio244073b0"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.81.6.1053"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)46707-X"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(89)82793-6"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.23.9411"},{"key":"e_1_2_7_20_1","first-page":"1227","article-title":"Pharmacological characterization of five cloned voltage\u2010gated K+ channels, Kv1.1, Kv1.2, Kv1.3, Kv1.5, and Kv3.1, stably expressed in mammalian cell lines","volume":"45","author":"GRISSMER S.","year":"1994","journal-title":"Mol. 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