Two types of 4-aminopyridine-sensitive potassium current in rabbit Schwann cells

Abstract

1. Delayed rectifier K+ currents were studied in Schwann cells cultured from neonatal rabbit sciatic nerves with the whole-cell patch-clamp technique. 2. Depolarizing voltage steps (40 ms duration) activated two types of K+ current: type I, whose apparent activation threshold was about -60 mV (half-maximal conductance at -40 +/- 1 mV, n = 10); and type II, whose apparent activation threshold was about -25 mV (half-maximal conductance at + 11 +/- 1 mV, n = 9). 3. Type I current was blocked by alpha-dendrotoxin (alpha-DTX) with an apparent equilibrium dissociation constant (KD) of 1.3 nM, whereas the type II current was unaffected by exposure to 500 nM toxin. The action of alpha-DTX on the type I current was reversible. 4. Most cells exhibited both types of current, but occasionally some cells displayed just type I or just type II. 5. Type I current activated rapidly and then showed a much slower fade, which became more noticeable with larger depolarizations. Activation of type II current was slower than that of type I and depended less steeply on voltage. The time constants of activation for type I and type II currents were derived with a Hodgkin-Huxley formalism (based on second-power activation and deactivation kinetics). The longest activation time constant for type II gating was more than twice the corresponding time constant for type I; however, the time constants determined from tail current decays at potentials more negative than -60 mV were shorter for the type II currents than for the type I currents. 6. Both type I and type II currents were sensitive to micromolar concentrations of 4-aminopyridine (4-AP). The KD for 4-AP blockade of type II current was 630 microM (pH 7.2, membrane potential (Em) = -10 mV), which is about 6 times higher than the corresponding value for 4-AP blockade of type I current at negative membrane potentials. The differential sensitivity of the type I and type II currents to 4-AP may account for the apparent voltage dependence of 4-AP block of delayed rectifier K+ currents. 7. In addition to types I and II, a third type of outward K+ current (type III) was generated in most cells at positive membrane potentials. This latter current was insensitive to millimolar concentrations of 4-AP. 8. Similarities between Schwann cell and neuronal potassium channels are discussed.