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J Appl Physiol (June 7, 2002). doi:10.1152/japplphysiol.01146.2001
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Articles in PresS, published online ahead of print June 7, 2002
J Appl Physiol, 10.1152/jap.01146.2001
Submitted on November 19, 2001
Accepted on May 31, 2002

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

Asma Yaghi1, Sanjay Mehta2, and David G McCormack2*

1 Pharmacology and Toxicology, University of Western Ontario, London, ON, Canada; Medicine/Respirology, London Health Sciences Centre, London, ON, Canada
2 Medicine/Respirology, London Health Sciences Centre, London, ON, Canada; Pharmacology and Toxicology, University of Western Ontario, London, ON, Canada

* To whom correspondence should be addressed. E-mail: david.mccormack{at}lhsc.on.ca.

We investigated the role of potassium channels in the attenuated pulmonary artery (PA) contractility characteristic of acute Pseudomonas pneumonia. 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 potassium chloride (KCl), phenylephrine (PE) or prostaglandin F2{alpha} (PGF2{alpha}) on PA rings before and after treatment with potassium (K+) channel blockers. In rings from pneumonia rats, paxilline (10µM), tetraethylammonium (TEA, 2mM) (blockers of large-conductance Ca2+-activated K+ channels (BKCa), and glybenclamide (KATP channel blocker, 80µM) had no significant effect on the attenuated contractile responses to KCl, PE and PGF2{alpha}. However, 4-aminopyridine (4-AP, 2mM), a blocker of voltage-gated K+ channels (KV, delayed rectifier K+ channel) reversed this depressed contractility. Therefore, BKCa and KATP channels do not contribute to the attenuated PA contractility observed in this model of acute pneumonia. In contrast, 4-AP enhances contraction in PA rings from pneumonia lungs, consistent with involvement of a KV channel in the depressed PA contractility in acute pneumonia. Unraveling the precise mechanism of attenuated contractility in pneumonia could lead to innovative selective therapies.




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