Effects of 4-aminopyridine and tetraethylammonium chloride on the electrical activity and cable properties of canine tracheal smooth muscle.
The actions of 4-aminopyridine (4-AP) on passive membrane properties of canine tracheal smooth muscle were compared to those of tetraethylammonium chloride (TEA). Transmembrane potential was studied with intracellular electrodes in a partitioned bath by extracellular current injection. The cells were electrically quiescent and showed rectification to depolarizing pulses. TEA (30 mM) depolarized the muscle and increased membrane resistance, time constant (282-421 msec), space constant (2.16-2.67 mm), decreased rectification and generated action potentials. D600, with TEA, abolished the spikes but further increased the membrane resistance, time constant (690 msec) and space constant (3.79 mm). TEA apparently blocked potassium conductance and initiated Ca++-dependent spikes owing to depolarization. 4-AP (5 mM) depolarized the membrane, but caused slow oscillations, decreased membrane resistance and space constant (1.94 mm), without affecting the time constant (265 msec) or rectification. These membrane effects of 4-AP were reversed to a large extent by atropine (10(-7) to 10(-6) M). D600 blocked the 4-AP-induced oscillations but not the decreased membrane resistance or space constant. 4-AP produced characteristic electrical and mechanical responses in a sucrose gap chamber when the muscle was functionally denervated by tetrodotoxin or scorpion venom. 4-AP appeared to activate the muscarinic receptor of canine trachealis to increase conductance, possibly to Na+ and K+. An effect on potassium conductance blockade might have been masked by the muscarinic receptor gated conductance changes, but is unlikely as it was not evident after exposure to atropine. We conclude that 4-AP actions in canine trachealis reflect chiefly activation of muscarinic receptors and not interference with potassium conductance.
D015761:4-Aminopyridine; D000109:Acetylcholine / Q000494:pharmacology; D000631:Aminopyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001665:Binding Sites; D004285:Dogs; D005260:Female; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013997:Time Factors; D014132:Trachea
D000631:Aminopyridines; D007473:Ion Channels; D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D005711:Gallopamil; D001285:Atropine; D015761:4-Aminopyridine; D000109:Acetylcholine; D011188:Potassium