SUMMARY1. In voltage clamped myelinated fibres, the K+ current was recorded in high-K+ media to allow analysis without complications due to K+ accumulation.2. After a depolarization, the tail of K+ current following repolarization decreases in two phases: a fast phase lasting about 20 msec and a slow exponential phase lasting several hundred milliseconds. When the duration of the depolarization is increased, the amplitude at time zero of the fast phase increases (activation of the conductance) and then decreases slowly (inactivation of the conductance). Simultaneously, the amplitude of the slow phase, extrapolated to time zero of repolarization, increases slowly and reaches a steady-state level (about 20 % of the maximum instantaneous current) after about 600 msec of depolarization.3. The fast phase of the tail current is blocked by external application of 4-aminopyridine (4-AP) (KD = 10-5 M). The slow phase is unaltered by 4-AP (I07-1_10-2 M).4. In the presence of 4-AP (10-3M), the remaining slow K+ current, activated by depolarizations, does not inactivate.5. During depolarizations and repolarizations, the conductance of the slow current (0Ks) (r = 45 sec at E = 0 mV); one component (GKr2) activating between -40 mV and + 30 mV and inactivating slowly (r = 2 sec at E = 0 mV). t = 12 0C.8. The maximum slow and fast conductances increase with [K]0. While the maximum fast conductance tends to saturate at high external K+ concentrations, the maximum slow conductance shows no sign of saturation. 9. A comparison between motor and sensory fibres shows that, while the amplitude of maximum slow and fast conductances are identical for both types of fibres, the amplitude of fast-I conductance is larger and consequently the amplitude of fast-2 is smaller in motor than in sensory fibres. The different spike frequency adaptations observed on both types of fibres are discussed in relation to these different relative fast conductances amplitudes.10. It is concluded that the K+ conductance of the nodal membrane is composed of three components (GKs' GKF, and GKf2) corresponding to three different and distinct types of K+ channels.

No abstract

A variety of studies have suggested that K+ channel activity is a key determinant for cell progression through the G1 phase of mitosis. We have previously proposed that K+ channels control the activity of cell cycle‐regulating proteins via regulation of cell volume. In order to test this hypothesis, we measured, with a Coulter counter and under different experimental conditions, the volume and rate of proliferation of neuroblastoma × glioma hybrid NG108‐15 cells. The K+ channel blockers TEA (1‐10 mM), 4‐aminopyridine (0.2‐2 mM) and Cs+ (2.5‐10 mM) increased the cell volume and decreased the rate of cell proliferation. Proliferation was fully inhibited when cell volume was increased by 25 %. A 40 % increase in the culture medium osmolarity with NaCl induced a 25 % increase in cell volume and an 82 % decrease in the rate of cell proliferation. A 40 % increase in the culture medium osmolarity with mannitol induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell proliferation. The Cl− channel blocker NPPB (5‐nitro‐2‐(3‐phenylpropylamino) benzoic acid; 50 μM) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation. A 24 % reduction in the culture medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation. Under whole‐cell patch‐clamp conditions, antibiotics (penicillin plus streptomycin) decreased the voltage‐dependent K+ current. Omission of antibiotics from the culture medium induced a 10 % decrease in the cell volume and a 32 % increase in the rate of cell proliferation. These results suggest that the mechanisms controlling cell proliferation are strongly influenced by the factors which determine cell volume. This could take into account the role in mitogenesis of K+ channels and of other ionic pathways involved in cell volume regulation.

No abstract