β‐Adrenoceptor subtypes and the opening of plasmalemmal K+‐channels in trachealis muscle: electrophysiological and mechanical studies in guinea‐pig tissue
Authors: Cook S.J. , Small R.C. , Berry J.L. , Chiu P. , Downing S.J. , Foster R.W. 
Published: July 2012

Mechanical and electrophysiological studies of guinea‐pig isolated trachealis have been made with the objectives of (a) identifying which of the β‐adrenoceptor subtypes mediates the opening of plasmalemmal K+‐channels, (b) gaining further insight into the properties of the novel, long‐acting β‐adrenoceptor agonist, salmeterol and (c) clarifying the role of K+‐channel opening in mediating the relaxant actions of agonists at β‐adrenoceptors.
Noradrenaline (10 nm–100 μm) caused a concentration‐dependent increase in the rate of beating of guinea‐pig isolated atria. The selective β1‐adrenoceptor blocking drug, CGP 20712A (100 nm–10 μm) caused concentration‐dependent antagonism of noradrenaline. The selective β2‐adrenoceptor blocking drug, ICI 118551, also produced concentration‐dependent antagonism of noradrenaline, but only when used in concentrations greater than 300 nm.
Cromakalim (100 nm–10 μm), isoprenaline (1–100 nm), procaterol (0.1–30 nm), salbutamol (1 nm– 1 μm), salmeterol (1–100 nm) and theophylline (1 μm– 1 mm) each caused concentration‐dependent suppression of the spontaneous tone of guinea‐pig isolated trachealis.
ICI 118551 (10 nm– 1μm) antagonized isoprenaline, procaterol and salmeterol in suppressing the spontaneous tone of the isolated trachea. The antagonism was concentration‐dependent. In contrast, ICI 118551 (1 μm) antagonized neither cromakalim nor theophylline. CGP 20712A (up to 1 μm) failed to antagonize cromakalim, isoprenaline, procaterol, salmeterol or theophylline. In trachea treated with indomethacin (2.8 μm) and carbachol (10 μm), salmeterol (1 μm) antagonized the effects of isoprenaline but not aminophylline.
Intracellular electrophysiological recording from guinea‐pig isolated trachealis showed that the relaxant effects of cromakalim (10 μm), isoprenaline (100 nm), procaterol (10 nm) and salbutamol (10nm −1 μm) were accompanied by the suppression of spontaneous electrical slow waves and by cellular hyperpolarization. In contrast, the relaxant effects of salmeterol (10 nm–1 μm) were not accompanied by significant cellular hyperpolarization.
CGP 20712A (1 μm) inhibited the hyperpolarization but not the relaxation induced by isoprenaline (100 nm). In contrast ICI 118551 (100 nm) inhibited both the hyperpolarization and the relaxation induced by isoprenaline (100 nm). Neither CGP 20712A (1 μm) nor ICI 118551 (100 nm) inhibited the hyperpolarization induced by cromakalim (10 μm). Salmeterol (1 μm) inhibited the hyperpolarization induced by isoprenaline (100 nm) but not that induced by cromakalim (10 μm).
It is concluded that activation of either β1‐ or β2‐adrenoceptors can promote the opening of K+‐channels in the trachealis plasmalemma. The poor ability of salmeterol to hyperpolarize trachealis muscle reflects neither its selectivity in activating β2‐adrenoceptors as opposed to β1‐adrenoceptors nor a non‐specific action in stabilizing the cell membrane. Instead, it may reflect low intrinsic efficacy of the drug at β2‐adrenoceptors. The opening of plasmalemmal K+‐channels plays a supportive rather than a crucial role in mediating the tracheal relaxant actions of agonists at β‐adrenoceptors.