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 α(1)- and α(2)-adrenoceptors to the NAD. The α(1)-adrenoceptor antagonist, prazosin (0.1μM), and the α(2)-antagonist, rauwolscine (1μM), reduced the amplitude of the NAD and in combination these agents virtually abolished the NAD. The K(ATP) channel blocker, glibenclamide (10μM) abolished the α(2)-adrenoceptor-mediated component of the NAD, indicating that activation of these receptors produces closure of K(ATP) channels. The α(1)-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 α(1)-adrenoceptor-mediated depolarization, indicating a decrease in membrane conductance; i.e. closure of K(+) channels. Broad-spectrum K(+) channel blockers (tetraethylammonium, 4-aminopyridine, Ba(2+)) and the TASK-1K(+) channel blocker, anandamide (10μM), did not reduce the α(1)-adrenoceptor-mediated NAD. The α(1)-adrenoceptor-mediated NAD was unaffected by the Cl(-) channel blockers, 9-anthracene carboxylic acid (100μM) and niflumic acid (10μM) or by the non-selective cation channel blocker, SKF 96365 (10μM). These findings indicate that the NAD is produced by activation of both α(1)-and α(2)-adrenoceptors. The α(2)-adrenoceptor-mediated component is produced by closure of K(ATP) channels whereas the α(1)-adrenoceptor-mediated component is most likely mediated by closure of another type of K(+) channel.