[Background] It is reported that natriuretic peptides affect the action potential and ICaL in cardiomyocytes via an increase in cGMP by activation of particulate guanylate cyclase (pGC). Uroguanylin (uro) is known to increase cGMP through pGC. In this study, we examined the effects of uro on ICaL in cardiomyocytes.
[Methods] Ventricular cells were isolated from guinea-pig hearts. The ICaL was recorded by use of whole-cell patch clamp method.
[Results] When uro was applied to the myocytes while raising its concentration (3 nM～0.3 M) after stimulating ICaL by 0.3 M isoproterenol (iso), the stimulated- ICaL was inhibited by uro on the whole. However, uro sometimes augmented the stimulated- ICaL. The basal ICaL was not affected by uro. ODQ, a selective soluble GC inhibitor, 0.1 mM did not exert the inhibitory effect on the action of uro. Rp-8-Br-PET-cGMPs (Rp), one of the most potent cGMP-PKG inhibitor, 10 M in patch pipette did not affect either, however, the uro-evoked augmentation of the stimulated- ICaL was not observed in the presence of Rp.
[Conclusion] Uroguanylin exerted the inhibitory effects on the iso-stimulated ICaL in a lot of cases, but its effects were not consistent. The mechanism of the uro-induced activation of pGC and ICaL remained to be elucidated