When corpus cavernosum smooth muscle cells (CCSMC) relax, the corporal sinuses fill with blood causing penile erection. Thus knowledge of the mechanisms that cause corpus cavernosum relaxation is essential for understanding and treating erectile dysfunction. Although NO/cGMP is the main inhibitory pathway involved in penile erection, when the NO receptor is knocked out other pathways can compensate (Groneberg et al. 2013). One possibility is that cAMP production, in response to agonist such as adenosine, VIP or PGE1 may mediate relaxation. However, the effects of cAMP on CCSMC have not been adequately characterised. The aim of this study, therefore, was to characterise the effects of cAMP on spontaneous Ca2+-activated Cl- currents, spontaneous depolarisations and Ca2+ events in isolated CCSMC. All of the experiments were approved by DkIT Animal Care Committee. Male New Zealand white rabbits were euthanized with pentobarbitone (iv) and their corpora cavernosum removed. CCSMC were isolated with collagenase and perfused with physiological saline at 37oC. Their electrical events were studied using the patch clamp technique, and their intracellular Ca2+ events were recorded by loading them with Fluo-4AM (500 nM) and imaging with an EMCCD camera attached to a spinning disk confocal microscope. When CCSMC were voltage clamped at -60 mV, they developed regular spontaneous transient inward currents (STICs), mediated by Cl- channels. 8-Br-cAMP (1 mM) reduced their amplitude from 193± 33pA to 62±39 pA (n=5, P<0.05) and frequency from 20.4 ±6.6/min to 6.4±3.0/min (P<0.05). Forskolin (1 µM) also decreased the frequency from 41.0 ± 13.6 to 14 ± 5.0/min (P<0.05, n=5), but increased amplitude from 323±102 pA to 613±153 pA (P<0.05). When held in current clamp mode, the cells developed regular spontaneous transient depolarisations (STDs). There were reduced in frequency both by 8-Br-cAMP (from 26.4±8.2/min to 11.6±6.1/min, n=5, P<0.05) and forskolin (from 42.4±10.8/min to 12.0±6.1/min, n=5, P<0.05), but both drugs increased the mean duration at half maximum amplitude (8-Br-cAMP from 140±60 ms to 309±136 ms, n=5, P<0.05; forskolin from 340±111 ms to 557±95, n=4, p<0.05). CCSMC also developed robust global intracellular Ca2+ events that extended along the entire length of the cell. These were also inhibited by 8-Br-cAMP, which reduced their frequency from 15.6±2.9/min to 2.7±1.2/min, (n=5, p<0.05) and reduced basal Ca2+ (F/F0) from 1 to 0.70±0.04 (P<0.05, Wilcoxon). Similarly, forskolin decreased frequency from 19.8±3.4/min to 6.0±1.5/min (n=6, P<0.05) and basal Ca2+ from 1 to 0.66±0.04 (n= 6, P<0.05). These results suggest that cAMP may reduce tone in CCSMC by inhibiting spontaneous pacemaker activity. This is similar to the action of NO/cGMP described previously (Sergeant et al. 2009).