Ionic mechanisms underlying electrical slow waves in canine airway smooth muscle
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In canine bronchial smooth muscle (BSM), spasmogens evoke oscillations in membrane potential ("slow waves"). The depolarizing phase of the slow waves is mediated by voltage-dependent Ca2+ channels; we examined the roles played by Cl- and K+ currents and Na+-K+-ATPase activity in mediating the repolarizing phase. Slow waves were evoked using tetraethylammonium (25 mM) in the presence or absence of niflumic acid (100 microM; Cl- channel blocker) or ouabain (10 microM; block Na+-K+-ATPase) or after elevating external K+ concentration ([K+]) to 36 mM (to block K+ currents); curve fitting was performed to quantitate the rates of rise/fall and frequency under these conditions. Slow waves were markedly slowed, and eventually abolished, by niflumic acid but were unaffected by ouabain or high [K+]. Electrically evoked slow waves were also blocked in similar fashion by niflumic acid. We conclude that the repolarization phase is mediated by Ca2+-dependent Cl- currents. This information, together with our earlier finding that the depolarizing phase is due to voltage-dependent Ca2+ current, suggests that slow waves in canine BSM involve alternating opening and closing of Ca2+ and Cl- channels.
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