EFFECTS OF 4-AMINOPYRIDINE AND TETRAETHYLAMMONIUM CHLORIDE ON THE ELECTRICAL-ACTIVITY AND CABLE PROPERTIES OF CANINE TRACHEAL SMOOTH-MUSCLE

Abstract

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 ms), space constant (2.16-2.67 mm), decreased rectification and generated action potentials. D600 [methoxyverapamil], with TEA, abolished the spikes but further increased the membrane resistance, time constant (690 ms) and space constant (3.79 mm). TEA apparently blocked K conductance and initiated Ca2+-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 rate constant (265 ms) or rectification. These membrane effects of 4-AP were reversed to a large extent by atropine (10-7-10-6 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 K 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. Apparently, 4-AP actions in canine trachealis chiefly reflect chiefly activation of muscarinic receptors and not interference with K conductance.