Abstract
In rat tail artery, activation of postjunctional alpha(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 microm) and PNU 37883A (5 microm), depolarized the smooth muscle and increased membrane resistance. Conversely, the K(ATP) channel openers, pinacidil (0.1 and 0.5 microm) and levcromakalim (0.1 microm), hyperpolarized the smooth muscle and decreased membrane resistance. Activation of K(ATP) channels with calcitonin gene-related peptide (CGRP; 10 nM) 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 mM), which would be expected to block K(ATP) channels, abolished the NAD, whereas teteraethylammonium (1 mM) and 4-aminopyridine (1 mM) increased its amplitude. Apamin (0.5 microm) and a lower concentration of Ba(2+) (0.1 mM) did not affect the NAD. These findings indicate that activation of alpha(2)-adrenoceptors by neurally released NA depolarizes the membrane of vascular smooth muscle by inhibiting K(ATP) channels open in the resting membrane.