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"familyName" : "Stocker", "givenName" : "M.", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 88241013, "link" : "/api/authorship/88241013", "label" : "Pedarzani, P. ✉", "listPosition" : 5, "share" : 0.0, "first" : false, "last" : true, "corresponding" : true, "familyName" : "Pedarzani", "givenName" : "P.", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true } ], "title" : "Benzamil inhibits neuronal and heterologously expressed small conductance Ca2+-activated K+ channels", "identifiers" : [ { 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dendrites of pyramidal neurons in the neocortex and hippocampal formation, where they participate in the local regulation of membrane excitability and synaptic signals. Through their inter-play with Ca2+ channels, SK channels regulate Ca2+ influx triggered by back-propagating action potentials in dendrites. Inhibition of SK channels affects both the amplitude and duration of Ca2+ transients, but the role of Ca2+ clearance mechanisms and their link to SK channel activity has not been established. Here we report the effect of the Na+/Ca2+ exchanger (NCX) inhibitor benzamil on Ca2+ extrusion and SK channels in the regulation of dendritic Ca2+ signals. Benzamil increased the duration and amplitude of dendritic Ca2+ transients elicited by back-propagating action potentials in hippocampal pyramidal neurons. This data is consistent with previous studies with SK channel blockers and suggests that benzamil inhibits SK channels in addition to the Na+/Ca2+ exchanger. Here we show that indeed both the neuronal SK-mediated IAHP current and the currents mediated by heterologously expressed SK channels were inhibited by benzamil. The inhibition of recombinant SK channels was seen with different K+ concentration gradients, and was stronger at negative voltages. The suppression of SK channels by benzamil is consistent with previous findings on the modulation of Ca2+ signals by SK channels in neurons. We additionally show that benzamil inhibits neuronal voltage-gated calcium currents. The results prompt a careful reassessment of the effects of benzamil on Ca2+ transients in native systems, given the spectrum of ion channels and exchangers this compound targets within a similar range of concentrations. © 2019 Elsevier Ltd", "keywords" : [ { "otype" : "Keyword", "mtid" : 1070305, "link" : "/api/keyword/1070305", "label" : "benzamil", "published" : true, "oldId" : 1070305, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1516828, "link" : "/api/keyword/1516828", "label" : "SK channel", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1551352, "link" : "/api/keyword/1551352", "label" : "CALCIUM TRANSIENT", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1576704, "link" : "/api/keyword/1576704", "label" : "calcium extrusion", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1608966, "link" : "/api/keyword/1608966", "label" : "hippocampal neuron", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1784297, "link" : "/api/keyword/1784297", "label" : "Backpropagating action potential", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2019, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : null, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2024-02-26", "oaFree" : false, "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 3, "citedCount" : 3, "ratings" : [ { "otype" : "SjrRating", "mtid" : 10872780, "link" : "/api/sjrrating/10872780", "label" : "sjr:D1 (2019) Scopus - Pharmacology NEUROPHARMACOLOGY 0028-3908 1873-7064", "listPos" : 30, "rankValue" : 0.1, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 3004, "link" : "/api/classificationexternal/3004", "label" : "Scopus - Pharmacology", "published" : true, "oldId" : 3004, "snippet" : true }, "ranking" : "D1", "calculation" : "DIRECT", "published" : true, "snippet" : true } ], "ratingsForSort" : "D1", "referenceList" : "Badarau, E., Dilly, S., Wouters, J., Seutin, V., Liegeois, J.F., Chemical modifications of the N-methyl-laudanosine scaffold point to new directions for SK channels exploration (2014) Bioorg. 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