Ionic basis for the electroresponsiveness of guinea-pig ventromedial hypothalamic neurones in vitro

The difference between the ionic bases for electroresponsiveness in the three types of neurone in the ventromedial hypothalamic nucleus (v.m.h.) were studied in in vitro brain slice preparations of the guinea-pig. The current-voltage relationships in all three types of neurone showed anomalous rectification. Application of tetrodotoxin (TTX) abolished the fast action potentials in all three types of cell. In type A cells, injections of outward current pulses did not evoke spikes when the cells were perfused with TTX alone, but the addition of tetraethylammonium chloride elicited broad spikes. In type B and C cells, broad spikes could be evoked with TTX alone. These results suggest the presence of a minimal high-threshold Ca2+ current in type A neurones, and a more prominent one in type B and C neurones. In type B neurones, Ca2+ conductance blockage with Mn2+ or Co2+, or replacement of Ca2+ by Mg2+, abolished the low-threshold response (l.t.r.). Substitution with Ba2+ did not increase the duration of the l.t.r. significantly, suggesting that under normal conditions the falling phase of the response was caused by inactivation of Ca2+ conductance. In type B and C neurones, the amplitude and duration of the after-hyperpolarization (a.h.p.) following direct activation by long outward current pulses were markedly reduced in Ca2+-free solution. These findings indicate that a large component of this response was generated by the Ca2+-dependent K+ conductance increase. In type A cells the a.h.p. amplitude was originally small and was not affected by the above treatment, suggesting that the participation of this conductance was minimal in this type. In type C neurones, the membrane potential following an inward current pulse showed a delayed return to the base line. This delay was produced by transient K+ conductance, since it was reduced by 4-aminopyridine. The frequency-current (f-I) relation of the first interval in type A and C cells was scarcely affected in Ca2+-free solution, while the slope of the initial firing f-I curves in type B neurones which had the l.t.r. became flatter. Furthermore, the f-I curves of the third interval in type C cells became steeper in Ca2+-free solution. The data indicate that the distinct membrane characteristics related to the heterogeneity among cells in the v.m.h. can be attributed to their specific ionic mechanisms, with the type A neurones showing a minimal high-threshold Ca2+ current, the type B having l.t.r. and the type C having a transient K+ (IA) current.