A number of β-adrenoceptor blockers (eg. pindolol and CGP12177) cause cardiostimulation at high concentrations and have been contraindicated in the treatment of ischemic heart disease due to sympathomimetic effects (Podrid and Lown, 1982). Previously Freestone et al. (1999) showed that a non-conventional partial agonist, CGP12177 is pro-arrhythmic in paced mouse ventricular cells. Recently, it has been shown that CGP12177, in quiescent rat atrial cells, provokes an increase in spontaneous calcium (Ca2+) release events from the sarcoplasmic reticulum (SR) even in the presence of propranolol (Sam et al., 2012). These propranolol-insensitive effects have led to the designation of a new receptor subtype – the β1L-adrenoceptor (low affinity) distinct from the classical β1-adrenoceptor now called the β1H-adrenoceptor (high affinity). A non-selective β-blocker, bupranolol, blocks the β1L-adrenoceptor with moderate potency (Kaumann et al., 1998) and thus may inhibit pro-arrhythmic effects caused by CGP12177. In this study we have used bupranolol in quiescent rat atrial cells to investigate its effect on SR Ca2+ release stimulated by CGP12177. Atrial cells were isolated from WKY rats (Freestone et al., 2000) and were loaded with the Ca2+ fluorescent dye, fluo 4-AM (5µM). Ca2+ events within quiescent cells were imaged in whole cell and line scanning mode of the LSM510 M confocal microscope. Cells were perfused with propranolol (200nM) alone, CGP12177 (1µM) in the presence of propranolol (200nM) and CGP12177 (1µM) in the presence and absence of bupranolol (1µM) and the frequency of calcium events recorded. Propranolol produced 0.4 ± 0.1 large but localised Ca2+ release events (wavelets) s-1. Co-administration of CGP12177 with propranolol significantly increased the incidence of wavelets to 0.86 ± 0.17 s-1 (n=12, p < 0.005). Perfusion with bupranolol alone and bupranolol with CGP12177 produced no wavelets. In terms of Ca2+ sparks, bupranolol produced an average of 27.4 ± 8.6 sparks s-1. Co-administration of bupranolol with CGP12177, elicited 47.6 ± 12.8 sparks s-1 but this difference was not statistically significant. In cells not exhibiting waves or wavelets, CGP12177 increased Ca2+ spark frequency (compared to propranolol perfusion alone) from 42 ± 5.3 s-1 to 62 ± 6.1 s-1 (n=6, p < 0.01). As shown previously, CGP12177 (working through β1L) isassociated with more potent arrhythmogenic effects in cardiomyocytes than for example, ISO (working through β1H). It can also be concluded that bupranolol inhibits spontaneous Ca2+ release activity mediated via β1L.