Figure 6.
Noradrenaline response involves a modulatory action on Ih. A, Pretreatment of the slice with the selective inhibitor of the Ih current, ZD7288 (20 μm, 20 min), abolished the Ih evoked by hyperpolarizing voltage steps (a). Accordingly, the depolarizing response to 50 μm NA was mostly reduced by 20 μm ZD7288 (b). B, Summary plot of the pharmacological analysis of the post-receptor mechanisms involved in β1-adrenoceptor-mediated response. The adenylate cyclase inhibitor SQ22,536 and the Ih blocker ZD7288 were the only drugs tested that were able to affect the NA-induced excitation. Conversely, a dopamine D1 receptor antagonist SCH23390 (10 μm) and two protein kinase A blockers, H-89 (10 μm) and KT-5720 (2 μm), failed to affect the response to NA. Likewise, the protein kinase C antagonist calphostin C (1 μm) the tyrosine kinase blocker genistein (30 μm), and the intracellularly applied PKG inhibitor 8-bromo-cGMP (10 μm) had no effect on the response to NA (*p < 0.01; **p < 0.001).