Inhibition of K ATP channels in the rat tail artery by neurally released noradrenaline acting on postjunctional α 2 ‐adrenoceptors

In rat tail artery, activation of postjunctional α 2 ‐adrenoceptors by noradrenaline (NA) released from sympathetic axons produces a slow depolarization (NAD) of the smooth muscle through a decrease in K + conductance. In this study we used intracellular recording to investigate whether the K + channel involved is the ATP‐sensitive K + (K ATP ) channel. Changes in membrane resistance were monitored by measuring the time constant of decay of excitatory junction potentials. The K ATP channel blockers, glibenclamide (10 μ m ) and PNU 37883A (5 μ m ), depolarized the smooth muscle and increased membrane resistance. Conversely, the K ATP channel openers, pinacidil (0.1 and 0.5 μ m ) and levcromakalim (0.1 μ m ), hyperpolarized the smooth muscle and decreased membrane resistance. Activation of K ATP channels with calcitonin gene‐related peptide (CGRP; 10 n m ) also hyperpolarized the smooth muscle and decreased membrane resistance. The NAD was abolished by both glibenclamide and PNU 37883A but was potentiated by CGRP. However, unlike CGRP, the directly acting K ATP channel openers, pinacidil and levcromakalim, inhibited the NAD. The effects of other K + channel blockers were also determined. A high concentration of Ba 2+ (1 m m ), which would be expected to block K ATP channels, abolished the NAD, whereas teteraethylammonium (1 m m ) and 4‐aminopyridine (1 m m ) increased its amplitude. Apamin (0.5 μ m ) and a lower concentration of Ba 2+ (0.1 m m ) did not affect the NAD. These findings indicate that activation of α 2 ‐adrenoceptors by neurally released NA depolarizes the membrane of vascular smooth muscle by inhibiting K ATP channels open in the resting membrane.