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 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.
Janssen
L J
LJ
Asthma Research Group and Smooth Muscle Research Program, Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Hague
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C
Nana
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D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D004285:Dogs; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D009991:Oscillometry; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
D015220:Calcium Channels; D018118:Chloride Channels; D015221:Potassium Channels; D009544:Niflumic Acid; D010042:Ouabain; D019789:Tetraethylammonium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium