Ionic mechanisms underlying electrical slow waves in canine airway smooth muscle

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 μM; Cl^- channel blocker) or ouabain (10 μM; 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.