Action potential (AP) alternans (AP-ALT) are linked to increased arrhythmogenesis. It is suggested that calcium (Ca2+) transient (CaT) alternans are the primary cause of AP alternans through a bi-directional coupling feedback mechanism because CaT alternans may develop in AP alternans free conditions. Supporting this notion to date, the counterpart scenario in which AP alternans develop in the absence of CaT alternans has not yet been demonstrated. With the objective of developing a CaT free AP alternans experimental model, we revisited the idea of inducing AP alternans in the presence of the Ca2+ buffer BAPTA and investigated if Bay K 8644, an L-type calcium channel agonist and known promoter of AP alternans, was effective in Ca2+ buffered cells. We analyzed AP-ALT incidence (positive when sequences of 14 or more APs exhibited repetitive short-to-long changes in AP duration (APD)) in isolated rabbit ventricle myocytes paced at progressively shorter cycles lengths (CL) from 1000 ms to the shortest CL > 179 ms eliciting AP-ALT to determine the alternans threshold (ALT-TH). We perfused Tyrode (37 oC) alone or with 25 nM Bay k 8644 upon freely contracting myocytes or in myocytes loaded (via patch microelectrode) with 10 or 20 mM BAPTA to completely abolish CaT. AP alternans developed abundantly in Ca2+ buffered myocytes (AP-ALT incidence 65 vs 80 vs 91%, in Controls vs 10 mM BAPTA vs 20 mM BAPTA, respectively). Controls and 10 mM BAPTA had similar ALT-TH (226±37 vs 269±88 ms, p>0.05) and alternans magnitude (13±5 vs 17±9 ms, p>0.05), but both parameters were larger in the 20 mM BAPTA myocytes (273±56 ms and 21±13 ms, respectively ALT-TH and alternans magnitude, p<0.05). Concomitantly, at ALT-TH, the diastolic interval (DI) was similar in all groups (46±17 ms vs 46±18 ms vs 49±10 ms, respectively Control vs 10 mM BAPTA vs 20 mM BAPTA, p>0.05), whilst APD was similar in Control and 10 mM BAPTA (180±34 vs 223±73 ms), but significantly larger in 20 mM BAPTA (225±52 ms, p<0.02 vs Controls). Delivery of Bay K 8644 to paced alternans free myocytes loaded with BAPTA elicited APD prolongation followed by crescendo alternans (APD beat-to-beat changes of progressively increasing amplitude leading to loss of 1:1 capture) in 11/11 myocytes (CL=300 ms) and 6/6 myocytes (CL=1000 ms). In the absence of CaT AP-ALT thrive and are more sensitive to activation rate changes and/or drugs promoting alternans. Therapies aiming to reduce CaT or its dynamic response should consider this.