THE PHARMACOLOGICAL PROPERTIES OF K-MUSCLE CELLS( CURRENTS FROM RABBIT ISOLATED AORTIC SMOOTH)

1 Using the whole-cell patch-clamp technique, the effects of several K + channel blocking drugs on K+ current recorded from rabbit isolated a ortic smooth muscle cells were investigated. 2 Upon depolarization fro m -80 mV, outward K+ current composed of several distinct components w ere observed: a transient, 4-aminopyridine (4-AP)-sensitive component (I-t) and a sustained component (I-sus), comprising a 4-AP-sensitive d elayed rectifier current (I-K(V)), and a noisy current which was sensi tive to tetraethylammonium (TEA), and probably due to Ca2+-activated K + current (I-K(Ca)). 3 Several drugs in clinical or experimental use h ave as part of their action an inhibitory effect on specific K+ channe ls. Because of their differential K+ channel blocking effects, these d rugs were used in an attempt to characterize further the K+ channels i n rabbit aortic smooth muscle cells. Imipramine, phencyclidine, sotalo l and amitriptyline failed to block selectively any of the components of K+ current, and were thus of little value in isolating individual c hannel contributions. Clofilium showed selective block of I-K(V) in th e presence of TEA, but only at low stimulation frequencies (0.07 Hz). At higher frequencies (1 Hz) of depolarization, both I-t and I-K(V) we re suppressed to a similar extent. Thus, the blocking action of clofil ium was use-dependent. 4 The voltage-dependent inactivation of I-t and the delayed rectifier were very similar although a brief (100 ms) pre -pulse to -30 mV could preferentially inactivate I-t. Together with th e non-selective blocking effects of the K+ channel blockers, similarit ies in the activation and inactivation of these two components suggest that they may not exist as separate ionic channels, but as distinct k inetic states within the same K+ channel population. 5 The effects of all of these drugs on tension were examined in strips of rabbit aorta. The non-specific K+ channel blockers caused only minor increases in b asal tension. TEA and 4-AP by themselves caused significant increases in tension and were even more effective when applied together. There a ppeared to be no correlation between the effects of the drugs tested o n tension and their actions on currents recorded from isolated myocyte s. Thus tension studies are an inappropriate means of investigating th e mechanism of action of these drugs, and studies on ionic currents in isolated myocytes cannot easily predict drug actions on intact tissue s.