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Adenosine (10 \u03bcmol\/L) caused a significant hyperpolarization (7\u00b11 mV) of AV nodal cells. Adenosine increased the occurrence and the rate dependence of activation failure (Wenckebach periodicity) of AV nodal cells; this effect was concentration dependent and mediated by A<jats:sub>1<\/jats:sub>adenosine receptors. The rate-dependent activation failure caused by adenosine was associated with a prolongation of the effective refractory period by 18\u00b12 ms (<jats:italic>P<\/jats:italic>&lt;.05), an increase in the duration of activation delay, and an elevation (from 0.22\u00b10.04 to 0.30\u00b10.03 nA,<jats:italic>P<\/jats:italic>&lt;.05) of the threshold current amplitude required to activate AV nodal cells. The results suggest that the slowed recovery of excitability of AV nodal cells caused by adenosine forms the cellular basis for adenosine-induced second-degree AV block. Adenosine decreased I<jats:sub>Ca,L<\/jats:sub>and activated I<jats:sub>K,ADO<\/jats:sub>of AV nodal cells. These actions of adenosine on ion currents may contribute to the effect of this nucleoside to depress excitability of AV nodal cells. The enhancement by adenosine of rate-dependent activation failure of AV nodal cells implies that the negative dromotropic effect of adenosine should be more pronounced during an episode of supraventricular tachycardia than during normal rhythm.<\/jats:p>","DOI":"10.1161\/01.res.78.4.697","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:47:05Z","timestamp":1339462025000},"page":"697-706","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Cellular Basis for the Negative Dromotropic Effect of Adenosine on Rabbit Single Atrioventricular Nodal Cells"],"prefix":"10.1161","volume":"78","author":[{"given":"Desuo","family":"Wang","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (D.W., L.B.) and Medicine (J.C.S., L.B.), University of Florida, Gainesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Shryock","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W., L.B.) and Medicine (J.C.S., L.B.), University of Florida, Gainesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Belardinelli","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (D.W., L.B.) and Medicine (J.C.S., L.B.), University of Florida, Gainesville."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","first-page":"209","volume":"12","year":"1925","unstructured":"Lewis T, Master AM. 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