INWARD RECTIFICATION AND ITS EFFECTS ON THE REPETITIVE FIRING PROPERTIES OF BULBOSPINAL NEURONS LOCATED IN THE VENTRAL PART OF THE NUCLEUS-TRACTUS-SOLITARIUS

1. An in vitro brain stem slice from adult guinea pigs was used to study the effects of membrane hyperpolarization in two classes of bulbospinal neurons, called types I and II, from the ventral parts of the nucleus tractus solitarius (vNTS). These bulbospinal neurons project to the phrenic motor nucleus and make up the dorsal respiratory group, a sensorimotor integrating area for rhythmic breathing movements. 2. Negative current injections (1 s long) were used in the discontinuous current-clamp mode to study the input resistance (R(in)) in both classes of bulbospinal vNTS neurons. The mean R(in) for type I neurons was 88.7 +/- 13.8 (SD) MOMEGA (n = 19) and for type 11 neurons was 92.6 +/- 14.0 MOMEGA (n = 16). Both classes of neurons displayed a depolarizing sag and inward rectification during negative current injections to membrane-potential levels less than or equal to -70 mV. The magnitude of the depolarizing sag became larger as the size of the negative current step was increased. On release from hyperpolarization, both cell types also exhibited a large anode break hyperpolarization (ABH). 3. The ABH was abolished in the presence of 5 mM 4-aminopyridine (4-AP), whereas the depolarizing sag and inward rectification were not affected. In the place of the ABH, a small postinhibitory rebound (PIR) depolarization was observed on release from hyperpolarization. The magnitude of PIR was dependent on the size of the depolarizing sag. In the presence of both 5 mM 4-AP and 5 mM Cs+, the depolarizing sag and PIR were completely blocked, whereas R(in) was increased. 4. The ionic currents underlying the ABH and depolarizing sag were directly observed by the use of the discontinuous single-electrode voltage-clamp technique. The ABH was caused by activation of an A-current (I(KA). The depolarizing sag was associated with a hyperpolarization-activated inward current (I(H)), which was activated at membrane-potential levels less than or equal to -70 mV. The peak amplitude of I(H) in type I neurons was -335 16 pA (n = 13) and in type II cells was -327 +/- 14 pA (n = 11 5. I(H) currents did not display inactivation during the hyperpolarizing voltage step. The I(H) current became larger when [K+]. was increased from 4 mM (control) to 12 mM and was blocked in the presence of 5 mM Cs+. The estimated reversal potential for the IH current was -41.5 +/- 4.8 mV (n = 8). 6. Inward tail currents associated with deactivation of I(H) were measured in solutions containing 5 mM 4-AP to block I(KA) currents and were completely blocked in the presence of 5 mM Cs+. Tail-current amplitudes were used to estimate the activation curve for I(H). In control solutions, I(H) was turned on at about -70 mV and was maximally activated at -100 to -120 mV. Half-maximal activation was estimated to be -88 mV. Increasing [K+]. to 12 mM did not shift the activation curve for I(H) along the voltage axis. 7. The I(H) current in vNTS neurons appeared similar to the mixed cation I(Q)-I(AR)-I(H) currents described in neurons and the I(H)-I(F)-I(K2) currents in heart cells. In vivo, I(H) currents would antagonize late expiratory phase synaptic inhibition and limit the degree to which dorsal respiratory group neurons cells could be hyperpolarized. An indirect consequence of this braking effect would be limiting the removal of inactivation from I(KA) currents, thereby restricting their expression during subsequent inspiratory phase depolarization.