Two transient outward currents in histamine neurones of the rat hypothalamus in vitro.

1. The transient outward current exhibited by the histamine neurones of the tuberomammillary nucleus was studied using the single-electrode voltage clamp technique in an in vitro rat hypothalamic slice preparation. 2. The transient outward current exhibited steady-state inactivation at the resting potential. Inactivation was removed by priming hyperpolarization with a V1/2 of -85 +/- 1.2 mV, while the V1/2 for activation was -60.3 +/- 2.1 mV. 3. The decay of the transient outward current was best fitted by two exponentials with time constants of 104 +/- 36 and 568 +/- 128 ms. These two components were provisionally termed IA,f and IA,s for the fast and slowly decaying currents, respectively. 4. Removal of inactivation was time dependent; inactivation was fully removed by hyperpolarizing pulses to -110 mV of 200 ms or greater duration. Removal of inactivation of IA,f was rapid, becoming complete with hyperpolarizing pre-pulses of 50 ms or greater, while removal of inactivation of IA,s was not complete until hyperpolarizing pre-pulses were 200 ms in duration. 5. The fast decaying current IA,f was selectively blocked by 1 mM-4-aminopyridine. Tetraethylammonium chloride (10 mM) had no effect on either IA,f or IA,s. 6. The inactivation curves for IA,s, determined both by using the values obtained from the amplitude of the computed slower exponential function as well as that of the current remaining in 1 mM 4-aminopyridine, were negative to those of IA,f. Similarly derived activation curves for IA,s were positive to those of IA,f. 7. Superfusion with a nominal 0 Ca2+ medium containing 10 mM-Mg2+ did not reduce the maximal transient outward current. 8. The reversal potential of IA,s with 2.5 mM-K+ in the medium was -95 +/- 3 mV; the reversal potential of IA,f was at least 15 mV negative to that of IA,s. 9. It is concluded that histaminergic tuberomammillary neurones possess at least two transient outward currents which can be distinguished on the basis of their rates of decay, 4-aminopyridine sensitivity, voltage dependence and reversal potentials.