Two mechanisms underlie the slow noradrenergic depolarization in the rat tail artery in vitro

In rat tail artery, short trains of electrical stimuli evoke both ATP-mediated excitatory junction potentials (EJPs) and a slow noradrenaline (NA)-mediated depolarization (NAD). Here we have investigated the contribution of α1- and α2-adrenoceptors to the NAD. The α1-adrenoceptor antagonist, prazosin (0.1 μM), and the α2-antagonist, rauwolscine (1 μM), reduced the amplitude of the NAD and in combination these agents virtually abolished the NAD. The KATP channel blocker, glibenclamide (10 μM) abolished the α2-adrenoceptor-mediated component of the NAD, indicating that activation of these receptors produces closure of KATP channels. The α1-adrenoceptor-mediated component of the NAD was increased in amplitude by glibenclamide. Changes in membrane conductance were monitored by measuring the time constant of decay of EJPs (τEJP). The τEJP was increased during α1-adrenoceptor-mediated depolarization, indicating a decrease in membrane conductance; i.e. closure of K+ channels. Broad-spectrum K+ channel blockers (tetraethylammonium, 4-aminopyridine, Ba2+) and the TASK-1 K+ channel blocker, anandamide (10 μM), did not reduce the α1-adrenoceptor-mediated NAD. The α1-adrenoceptor-mediated NAD was unaffected by the Cl− channel blockers, 9-anthracene carboxylic acid (100 μM) and niflumic acid (10 μM) or by the non-selective cation channel blocker, SKF 96365 (10 μM). These findings indicate that the NAD is produced by activation of both α1-and α2-adrenoceptors. The α2-adrenoceptor-mediated component is produced by closure of KATP channels whereas the α1-adrenoceptor-mediated component is most likely mediated by closure of another type of K+ channel.