Some β-adrenoceptor blockers, such as pindolol, cause cardiostimulation at high concentrations. Freestone et al (1999) have shown that CGP12177, a structurally similar molecule to pindolol, is 40 times more potent than isoprenaline (ISO) in causing arrhythmias in mouse ventricular myocytes. Pro-arrhythmic effect of CGP12177 occurs despite that it increases intracellular calcium levels by 30% of that caused by ISO. Furthermore, in ferret ventricle it has been shown that CGP12177 causes an increase in the plateau phase of the action potential whilst shortening the overall action potential duration more potently than noradrenaline acting on conventional β1-adrenoceptors (Lowe et al, 1998). This led to designation of a new receptor – the low affinity β1-adrenoceptor (β1L). The mechanism for arrhythmogenic effects mediated by this receptor is currently unknown. Rat atrial myocyte arrhythmias have previously been observed with endothelin due to calcium release via inositol 1, 4, 5-triphosphate receptors (IP3R) located on the SR (Li et al, 2005). In this study we used CGP12177 and a blocker of IP3R-mediated calcium release, 2-APB, in quiescent rat atrial cells to investigate effect of CGP12177 on intracellular calcium release. Atrial cells from WKY rats were loaded with Fluo 4-AM (5μM). Images of calcium events within quiescent cells were obtained using LSM510 Meta confocal microscope every 3ms. Cells were perfused with 2-APB (5μM) in the presence of propranolol (200nM) followed by 2-APB and propranolol in the presence of CGP12177 (1μM). 2-APB and propranolol perfusion caused 0.4 ± 0.2 large but spatially restricted calcium release events (wavelets) per second and 30.4 ± 4.3 calcium sparks per second (n=7 cells from 3 animals). CGP12177 with 2-APB and propranolol increased the incidence of wavelets to 1.9 ± 0.4 wavelets per second (p < 0.005) but did not alter frequency of calcium sparks. CGP12177 in the presence of propranolol increased the incidence of wavelets to 0.86 ± 0.17 wavelets per second compared to 0.4 ± 0.1 wavelets per second (p < 0.01) in the presence of propranolol alone (n = 12 cells, 6 animals). In cells which did not exhibit calcium waves or wavelets, CGP12177 (with propranolol) increased the incidence (p < 0.01) of calcium sparks from 42 ± 5.3 to 62 ± 6.1 per second (n = 6 cells from 6 animals). As shown previously for mouse ventricular myocytes, CGP12177 is associated with potent arrhythmogenic effects in rat atrial cells. This effect is not affected by addition of 2-APB which has been suggested to be effective in controlling spontaneous calcium release which might contribute to calcium-mediated atrial arrhythmias (Zima and Blatter, 2004). It can be concluded that arrhythmic events mediated by β1L are not the result of calcium release via IP3R.