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Disease of the sinus node and impairment of atrioventricular conduction induce an excessively low ventricular rate (bradycardia), which cannot meet the needs of the organism. Bradycardia accounts for about half of the total workload of clinical cardiologists. The \u2018sick sinus\u2019 syndrome (SSS) is characterized by sinus bradycardia and periods of intermittent atrial fibrillation. Several genetic or acquired risk factors or pathologies can lead to SSS. Implantation of an electronic pacemaker constitutes the only available therapy for SSS. The incidence of SSS is forecast to double over the next 50\u00a0years, with ageing of the general population thus urging the development of complementary or alternative therapeutic strategies. In recent years an increasing number of mutations affecting ion channels involved in sino\u2010atrial automaticity have been reported to underlie inheritable SSS. L\u2010type Ca<jats:sub>v<\/jats:sub>1.3 channels play a major role in the generation and regulation of sino\u2010atrial pacemaker activity and atrioventricular conduction. Mutation in the <jats:italic>CACNA1D<\/jats:italic> gene encoding Ca<jats:sub>v<\/jats:sub>1.3 channels induces loss\u2010of\u2010function in channel activity and underlies the sino\u2010atrial node dysfunction and deafness syndrome (SANDD). Mice lacking Ca<jats:sub>v<\/jats:sub>1.3 channels (<jats:italic>Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>) fairly recapitulate SSS and constitute a precious model to test new therapeutic approaches to handle this disease. Work in our laboratory shows that targeting G protein\u2010gated K<jats:sup>+<\/jats:sup> (<jats:italic>I<\/jats:italic><jats:sub>KACh<\/jats:sub>) channels effectively rescues SSS of <jats:italic>Ca<jats:sub>v<\/jats:sub>1.3<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic> mice. This new concept of \u2018compensatory\u2019 ion channel targeting shines new light on the principles underlying the pacemaker mechanism and may open the way to new therapies for SSS.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp7400-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>","DOI":"10.1113\/jp270678","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T08:57:13Z","timestamp":1467622633000},"page":"5869-5879","source":"Crossref","is-referenced-by-count":29,"title":["Rescuing cardiac automaticity in L\u2010type Cav1.3 channelopathies and beyond"],"prefix":"10.1113","volume":"594","author":[{"given":"Pietro","family":"Mesirca","sequence":"first","affiliation":[{"name":"D\u00e9partement de Physiologie Institut de 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