NON-NEUROGENIC ELECTRICALLY-EVOKED RELAXATION IN CANINE AIRWAY MUSCLEINVOLVES ACTION OF FREE-RADICALS ON K+ CHANNELS

Cyclopiazonic acid (selective blocker of the internal Ca++ pump) evoke d tonic contraction in canine bronchial smooth muscle (BSM) and trache al smooth muscle. This contraction was biphasic, including an initial component that was relatively insensitive to blockade of Ca++ influx ( e.g., removal of external Ca++; nifedipine; hyperpolarization using le makalim) followed by a component that was sensitive to all such interv entions. In BSM, but not in tracheal smooth muscle, electrical field s timulation (EFS) evoked relaxations that were not affected by interven tions designed to prevent release of autacoids from nerve endings or t he epithelium, Na+/Ca++ exchange or Ca++-ATPase activities (internal o r plasmalemmal). EFS evoked little or no relaxant response in carbacho l-precontracted BSM in the presence of propranolol. After Ca++ was rep laced with Sr++, however, carbachol evoked comparable contraction afte r which EFS evoked non-neurogenic relaxations. We found that the EFS-e voked relaxations were abolished by TEA or high KCl, were reduced sign ificantly by charybdotoxin or quinine, were reduced partially by ouaba in and were unaffected by removal of external K+, by apamin or by glyb enclamide. 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 observatio ns suggest that the cyclopiazonic acid-evoked contraction involves pha rmacomechanical coupling mechanisms (i.e., Ca++-release) initially, fo llowed by electromechanical coupling (i.e., voltage-dependent Ca++ inf lux). After depletion of the internal Ca++ store (e.g., by cyclopiazon ic acid or Sr++), EFS is able to evoke in BSM (but not in tracheal smo oth muscle) relaxations that seem to involve opening of K+ channels (i ncluding those of the large-conductance Ca++-dependent type) by EFS-li berated free radicals.