A slowly activating voltage-dependent K⁺ current in rat pituitary nerve terminals

1. A novel slowly activating voltage-dependent K⁺ current was observed in isolated nerve terminals from rat neurohypophysis using the whole-cell configuration of the patch-clamp technique. 2. The activation kinetics of the slow current could be fitted assuming Hodgkin-Huxley-type kinetics, an exponential, n, of 1.3 and activation time constants decreasing from 4 s at -50 mV to 0.7 s at +40 mV. 3. A positive shift of reversal potential was observed when [K⁺] was increased in the bath solution. The current is carried mainly but not exclusively by K⁺ ions. 4. When intracellular free [Mg²⁺] was low (~60 μM), average current density was 74 pA pF^-1 at membrane potentials around 0 mV. In 83% of nerve terminals current amplitude was > 20 pA pF^-1. 5. The slow current was never observed when the pipette contained 4.6 mM free Mg²⁺. At a physiological level of free Mg²⁺ (0.5 mM) the average current density was 16 pA pF^-1. 6. When nerve terminals were analysed after patch-clamp experiments for vasopressin content by immunodetection, no difference in current amplitude was found between the terminals containing vasopressin and all analysed terminals. 7. The voltage dependence of activation was fitted by a Boltzmann equation giving a half-activation potential of -37 mV and a slope factor of about 9 mV. 8. Tail current deactivation kinetics was biexponential with time constants of 0.12 and 1.5 s. Kinetics was dependent on the duration of the activating pulse. 9. Noise analysis of the slow current indicated a single-channel current of 0.33 pA at +6 mV, corresponding to a single-channel conductance of 4.3 pS. 10. This is the first demonstration of a current similar to the slow K⁺ current, I(Ks), in a neurone, suggesting that a protein similar to the I(Ks)-inducing channel protein I(sK) (minK) may be present in peptidergic nerve terminals. 11. The activation properties are consistent with and role of the slow current in inhibition of excitability, at least at the level of the nerve terminal.