Figure 3.

Pharmacology of the noradrenergic excitation of cholinergic interneurons. A, In the presence of TTX, the membrane depolarization caused by NA (30 μm) was mostly reduced when the slice was pretreated with betaxolol (10 μm) (a). Isoproterenol (30 μm), a β1-adrenoceptor agonist, mimicked the NA-induced membrane depolarization. B, Similarly, time-frequency histograms show the increase in number of action potentials induced by bath-applied NA (30 μm), prevented by pretreatment with the β1-adrenoceptor antagonist betaxolol (10 μm). Pretreatment with betaxolol is indicated by the interruption on the x-axis. C, Dose–response curve of the membrane depolarization, expressed as percentage of maximal response, caused by increasing doses of NA (0.3—1000 μm, filled circles) in control conditions and in the presence of betaxolol (10 μm, open triangles). The rightward shift revealed the competitive nature of its antagonism. The EC₅₀ for the NA response was dramatically increased in betaxolol, whereas the Hill slope did not differ significantly (for details, see Results). D, Summary plot of noradrenergic drugs tested on the NA-induced membrane depolarization: prazosin (0.3 μm), yohimbine (1 μm), propranolol (30 μm), and betaxolol (10 μm). ^*p < 0.01; ^**p < 0.001.