A SLOWLY ACTIVATING VOLTAGE-DEPENDENT K-TERMINALS( CURRENT IN RAT PITUITARY NERVE)

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 kin etics of the slow current could be fitted assuming Hodgkin-Huxley-type kinetics, an exponential, n, of 1 . 3 and activation time constants d ecreasing 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 bat h solution. The current is carried mainly but not exclusively by K+ io ns. 4. When intracellular free [Mg2+] was low (similar to 60 mu M), av erage 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 av erage current density was 16 pA pF(-1). 6. When nerve terminals were a nalysed after patch-clamp experiments for vasopressin content by immun odetection, no difference in current amplitude was found between the t erminals containing vasopressin and all analysed terminals. 7. The vol tage dependence of activation was fitted by a Boltzmann equation givin g 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 duratio n of the activating pulse. 9. Noise analysis of the slow current indic ated 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 demons tration of a current similar to the slow K+ current, I-Ks, in a neuron e, suggesting that a protein similar to the I-Ks-inducing channel prot ein I-sK (minK) may be present in peptidergic nerve terminals. 11. The activation properties are consistent with a role of the slow current in inhibition of excitability, at least at the level of the nerve term inal.