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Inhibition of glybenclamide-sensitive K+ channels underlies noradrenergic depolarization of the rat tail artery in vitro

J.H. Tan, J.A. Brock, Prince of Wales Medical Research Institute, Randwick, NSW, Australia

In rat tail artery, activation of α2-adrenoceptors by noradrenaline released from perivascular sympathetic axons produces a slow depolarization of the smooth muscle through a decrease in K+ conductance [1]. This study used intracellular recording to investigate whether neurally-released noradrenaline inhibits ATP-sensitive K+ (KATP) channels in this artery. Segments of proximal tail artery were isolated from female Wistar rats (∼8 week of age) anaesthetized with pentobarbital (100 mg/kg, i.p.) and exsanguinated. The tissues were mounted in a 1 ml recording chamber and intracellular recordings were made with glass microelectrodes (120 -200 MΩ). Changes in membrane conductance were monitored by measuring the time constant of decay of excitatory junction potentials. The KATP channel blocker, glybenclamide (10 μM), depolarized the smooth muscle and decreased membrane conductance. Conversely, both the KATP channel opener, pinacidil (0.1 and 0.5 μM), and calcitonin gene related peptide (10 nM; CGRP) hyperpolarized the smooth muscle and increased membrane conductance. The nerve-evoked slow depolarization was abolished by glybenclamide and was potentiated by CGRP. However, unlike CGRP, pinacidil had an inhibitory effect on the slow depolarization. These findings suggest that neurally-released noradrenaline inhibits the activity of KATP channels, resulting in membrane depolarization. We suggest the inhibitory action of activating α2-adrenoceptors on KATP channels is due to an inhibition of protein kinase A activity mediated through a reduction in cAMP levels [2].

(1) Cassell JF, McLachlan EM, Sittiracha T. (1988) J. Physiol. 397: 31-49.

(2) Hayabuchi Y, Davies NW, Standen NB. (2001) J. Physiol. 530:193-205.