The Electrophysiological Effects of Two Fenamates on Pulmonary Artery Smooth Muscle Cells

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The Electrophysiological Effects of Two Fenamates on Pulmonary Artery Smooth Muscle Cells

Proceedings of the British Pharmacological Society at http://www.pA2online.org/abstracts/Vol7Issue4abst057P.pdf The electrophysiological effects of two fenamates on pulmonary artery smooth muscle cells Yiwen Dong, Clio Evans, Alison Gurney. University of Manchester, Manchester, United Kingdom. The pulmonary arterial pressure is normally kept low. This is partly due to the opening of a group of K+ conducting channels expressed by the smooth muscle cells surrounding the pulmonary arteries (PASMC)1. The identity of these K+ channels is unknown, although experiments suggested them to include KCNQ channels2. The project aimed to determine the effects of two KCNQ channel openers, mefenamic acid and meclofenamic acid, on isolated rat pulmonary arteries and rat PASMC. The artery tension changes induced by the two drugs were measured by myography; changes in cell membrane potential, membrane resistance and ionic currents were detected using the patch clamp whole-cell configuration. The isolated arteries and cells were perfused during the experiments with physiological salt solution, with a composition (in mM): NaCl 122; KCl 5; MgCl2 1; NaH2PO4 0.5; KH2PO4 0.5; HEPES 10; glucose 11; CaCl2 1; pH adjusted to 7.3 using NaOH. Both mefenamic and meclofenamic acid caused vasodilation with EC50 values of 28 and 14 µM, respectively. Meclofenamic acid was also more potent at inducing membrane potential hyperpolarisation. Meclofenamic acid, at 25 µM, caused a significant change of -14 ± 2 mV (n=9) in membrane potential, whereas significant change of -8 ± 3 mV (n=7) was only observed at 50 µM of mefenamic acid. No drug-induced changes in membrane resistances and voltage-gated K+ currents were detected. The results supported the importance of KCNQ channels within the pulmonary arteries, although the drug effects on membrane resistance and ionic currents were difficult to interpret, due to non-selectivity of the drugs affecting other ion-conducting channels expressed by the PASMC. 1. Burg ED et al (2008) Br J Pharmacol 153:S99-111. 2. Joshi S et al (2009) J Pharmacol Exp Ther 329:368-376. .

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