Delayed rectifier potassium channels contribute to the depressed pulmonary artery contractility in pneumonia

Abstract

We investigated the role of K+ channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonaspneumonia. Contractility of PA rings from the lungs of control or pneumonia rats was assessed in vitro by obtaining cumulative concentration-response curves to the contractile agonists KCl, phenylephrine, or PGF2α on PA rings before and after treatment with K+ channel blockers. In rings from pneumonia rats, paxilline (10 μM), tetraethylammonium (2 mM) (blockers of large-conductance Ca2+-activated K+ channels), and glybenclamide (ATP-sensitive K+ channel blocker, 80 μM) had no significant effect on the attenuated contractile responses to KCl, phenylephrine, and PGF2α. However, 4-aminopyridine (2 mM), a blocker of voltage-gated K+channels (delayed rectifier K+ channel) reversed this depressed contractility. Therefore, large-conductance Ca2+-activated K+ and ATP-sensitive K+ channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-aminopyridine enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a voltage-gated K+ channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative therapies for the pulmonary vascular abnormalities associated with this disease.