Features of 4-aminopyridine sensitive outward current observed in single smooth muscle cells from the rabbit pulmonary artery

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Abstract
The 4-aminopyridine (4AP) sensitive outward current of enzymatically dispersed single smooth muscle cells of the rabbit main pulmonary artery were investigated using the voltage clamp method. When the cell was exposed to physiological salt solution (PSS) in the bath and high K+ in the pipette no inward current was generated by depolarization of the membrane, but when 4AP was present in the bath or when Cs+ with tetraethylammonium+ (Cs+-TEA+) in the pipette, an inward current was generated. This current was enhanced by Ba2+ or high Ca2+ and was blocked by inorganic or organic Ca2+ channel blockers. The outward current was partly inhibited by the Ca2+ channel blockers, Ca2+-free or Mn2+ containing solution. The residual outward current was blocked by external application of 10 mM 4AP, whereas it was inhibited by half with 100 mM TEA+. To investigate further natures of 4AP sensitive outward current, the following experiments were done in the bath solution containing 2.5 mM Mn2+. The reversal potential of this outward current, estimated from the tail current, remained the same in Na+-deficient solution, but shifted to near the K+-equilibrium potential in Cl− deficient solution. Thus, the main current carrier for the outward current seems to be K+, but Cl− may participate to some extent. The amplitude of the outward current decreased slowly. However, the reversal potential was not changed, suggesting the reduction in amplitude of the outward current was not due to the accumulation of K+ on the outer surface of the membrane. As 4AP inhibited the outward current to a greater extent at lower than higher membrane potential levels, 4AP bound to the channel may be dislodged at higher levels. When pH of the bath solution was modified from 7.3 to 8.0, inhibitory actions of 4AP were enhanced (pKa value of 4AP=9.17). Thus, a non-ionized form of 4AP may act as a channel blocker. We conclude that in smooth muscle cells of the pulmonary artery, lack of an action potential in physiological solution may partly be due to a small inward current as well as a large contribution of the 4AP sensitive outward current.