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The only currently available therapy for chronic SND is the implantation of an electronic pacemaker. Because of the growing burden of SND in the population, new pharmacological therapies of chronic SND and heart block are desirable. We developed a collection of genetically modified mouse strains recapitulating human primary SND associated with different degrees of AV block. These mice were generated with genetic ablation of L-type Ca<jats:sub>v<\/jats:sub>1.3 (Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup>), T-type Ca<jats:sub>v<\/jats:sub>3.1 (Ca<jats:sub>v<\/jats:sub>3.1<jats:sup>\u2212\/\u2212<\/jats:sup>), or both (Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup>\/Ca<jats:sub>v<\/jats:sub>3.1<jats:sup>\u2212\/\u2212<\/jats:sup>). We also studied mice haplo-insufficient for the Na<jats:sup>+<\/jats:sup> channel Na<jats:sub>v<\/jats:sub>1.5 (Na<jats:sub>v<\/jats:sub>1.5<jats:sup>+\/<\/jats:sup>) and mice in which the cAMP-dependent regulation of hyperpolarization-activated f-(HCN4) channels has been abolished (HCN4-CNBD). We analysed, by telemetric ECG recording, whether pharmacological inhibition of the G-protein-activated K<jats:sup>+<\/jats:sup> current (<jats:italic>I<\/jats:italic><jats:sub><jats:italic>KACh<\/jats:italic><\/jats:sub>) by the peptide tertiapin-Q could improve HR and AV conduction in these mouse strains. Tertiapin-Q significantly improved the HR of Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup> (19%), Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup>\/Ca<jats:sub>v<\/jats:sub>3.1<jats:sup>\u2212\/\u2212<\/jats:sup> (23%) and HCN4-CNBD (14%) mice. Tertiapin-Q also improved cardiac conduction of Na<jats:sub>v<\/jats:sub>1.5<jats:sup>+\/\u2212<\/jats:sup> mice by 24%. Our data suggest that the development of pharmacological <jats:italic>I<\/jats:italic><jats:sub><jats:italic>KACh<\/jats:italic><\/jats:sub> inhibitors for the management of SND and conduction disease is a viable approach.<\/jats:p>","DOI":"10.1038\/s41598-020-66673-8","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T10:05:07Z","timestamp":1592388307000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Inhibition of G protein-gated K+ channels by tertiapin-Q rescues sinus node dysfunction and atrioventricular conduction in mouse models of primary bradycardia"],"prefix":"10.1038","volume":"10","author":[{"given":"Isabelle","family":"Bidaud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony Chung You","family":"Chong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Carcouet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan De","family":"Waard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavien","family":"Charpentier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Ronjat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel De","family":"Waard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Isbrandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Wickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo E.","family":"Mangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mesirca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"66673_CR1","unstructured":"Semelka, M., Gera, J. & Usman, S. 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