Effects of tetraethylammonium and 4‐aminopyridine on outward currents and excitability in canine tracheal smooth muscle cells

Abstract

1 The effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on

Acetylcholine activates non‐selective cation and chloride conductances in canine and guinea‐pig tracheal myocytes.

“…8B). These resembled the spontaneous transient outward currents (STOCs) reported previously in intestinal and vascular smooth muscle (Benham et al 1985;Benham & Bolton, 1986;Komori & Bolton, 1990;Sims, Vivaudou, Biancani, Hillemeier, Singer & Walsh, 1990) and tracheal smooth muscle (Hisada, Kurachi & Sugimoto, 1990;Muraki, Imaizumi, Kojima, Kawai & Watanabe, 1990) and which were attributed to Ca2"-dependent K+ currents. However, another pattern of spontaneous currents was evident in approximately half of the cells studied (fourteen of twenty-one guinea-pig and five of fifteen canine cells): spontaneous transient inward currents at potentials negative to -30 mV which became biphasic (outward current preceding the more slowly decaying inward current) at -30 mV and more positive ( Fig.…”

“…The reversal of these currents close to EC1 and their dependence on Na+ suggest that they 214 ACh ACTIVATES CHLORIDE CURRENT IN TRACHEALIS involved Cl-and non-selective cation currents. These inward currents were coincident with STOCs which have been attributed in other smooth muscle systems to sporadic release of Ca2+ from the SR and subsequent activation Of IK(Ca) (Benham et al 1985;Benham & Bolton, 1986;Hisada et al 1990;Komori & Bolton, 1990;Muraki et al 1990;Sims et al 1990). Moreover, both the spontaneous inward currents and the STOCs were reversibly suppressed by ACh, possibly due to ACh-induced emptying of the SR.…”

“…After eliminating the contribution of Na', we found that increasing [Ca2+] (Kotlikoff, 1988;Hisada et al 1990;Muraki et al 1990). …”

“…That is, if ACh activated Ca2+ and/or Na+ channels alone, the membrane would be depolarized to extremely positive potentials, causing a large influx of Ca2 , since peak inward Ca2+ currents occur at 0 to + 10 mV in canine and guinea-pig tracheal myocytes (Kotlikoff, 1988;Hisada et al 1990;Muraki et al 1990). In contrast, opening of Clchannels and non-selective cation channels depolarizes the membrane to -20 to may be important from the point of view of the whole organism.…”

Effects of some K+‐channel inhibitors on the electrical behaviour of guinea‐pig isolated trachealis and on its responses to spasmogenic drugs

“…Furthermore, dofetilide exhibits selectivity of action in that it does not simultaneously inhibit the slowly activating component of the delayed rectifier K+-current, the inwardly rectifying K+-current, the fast Na+-current or the L-type Ca2+ current (Gwilt et al, 1991;Carmelite, 1992;Jurkiewicz & Sanguinetti, 1993;Kiehn et al, 1994 by more than 90% following the addition of 4-AP (1 mM) to the bathing medium. In other experiments using excised plasmalemmal patches of canine trachealis, the same concentration of 4-AP was without effect on the activity of BKCa channels (Muraki et al, 1990;Boyle et al, 1992). This suggests that, in airways smooth muscle, 4-AP exhibits some selectivity as an inhibitor of Kd, channels as opposed to BKCa.…”