Non-neurogenic electrically evoked relaxation in canine airway muscle involves action of free radicals on K+ channels.
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Cyclopiazonic acid (selective blocker of the internal Ca+2 pump) evoked tonic contraction in canine bronchial smooth muscle (BSM) and tracheal smooth muscle. This contraction was biphasic, including an initial component that was relatively insensitive to blockade of Ca+2 influx (e.g., removal of external Ca+2; nifedipine; hyperpolarization using lemakalim) followed by a component that was sensitive to all such interventions. In BSM, but not in tracheal smooth muscle, electrical field stimulation (EFS) evoked relaxations that were not affected by interventions designed to prevent release of autacoids from nerve endings or the epithelium, Na+/Ca+2 exchange or Ca(+2)-ATPase activities (internal or plasmalemmal). EFS evoked little or no relaxant response in carbachol-precontracted BSM in the presence of propranolol. After Ca+2 was replaced with Sr+2, however, carbachol evoked comparable contraction after which EFS evoked non-neurogenic relaxations. We found that the EFS-evoked relaxations were abolished by TEA or high KCI, were reduced significantly by charydotoxin or quinine, were reduced partially by ouabain and were unaffected by removal of external K+, by apamin or by glybenclamide. In addition, the relaxations were reduced significantly by the free radical scavenger N-acetylcysteine, were mimicked by H2O2 but were unaffected by superoxide dismutase or catalase. These observations suggest that the cyclopiazonic acid-evoked contraction involves pharmacomechanical coupling mechanisms (i.e., Ca(+2)-release) initially, followed by electromechanical coupling (i.e., voltage-dependent Ca+2 influx). After depletion of the internal Ca+2 store (e.g., by cyclopiazonic acid or Sr+2), EFS is able to evoke in BSM (but not in tracheal smooth muscle) relaxations that seem to involve opening of K+ channels (including those of the large-conductance Ca(+2)-dependent type) by EFS-liberated free radicals.
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