Ionic basis for endogenous rhythmic patterns induced by activation of N-methyl-D-aspartate receptors in neurons of the rat nucleus tractus solitarii

Abstract

1. Activation of N-methyl-D-aspartate (NMDA) receptors in caudal nucleus tractus solitarii (cNTS) neurons elicited endogenous rhythmic activities. We used an in vitro brain stem slice preparation to determine the ionic mechanisms underlying the generation of these activities. 2. Using intracellular recordings, we found several ionic conductances to be responsible for the electrophysiological properties of cNTS neurons. After addition of tetrodotoxin (TTX) to the perfusate, cNTS neurons were still able to generate action potentials (APs). Because these APs were suppressed by the addition of cobalt or by the reduction of calcium, they were likely due to calcium currents (ICa). In addition, the amplitude of the afterhyperpolarization (AHP) that followed a train of TTX-resistant APs was reduced in both low-calcium and cobalt-containing saline. It was therefore suggested that calcium-activated potassium (IKCa) currents were involved in the AHP. Accordingly, application of apamin, a blocker of slow IKCa, also decreased the AHP. cNTS neurons exhibited a delayed excitation phenomenon, characterized by a ramplike depolarization that delayed the onset of neuronal firing, when they were depolarized from hyperpolarizing potential. The underlying current was presumed to be an A-current (IKA), because this phenomenon was suppressed during application of 4-aminopyridine (4-AP). 3. Application of NMDA elicited different types of discharge patterns in cNTS neurons: a repetitive firing at depolarized levels of membrane potential (above -60 mV) and rhythmic patterns characterized by either rhythmic bursting or rhythmic single discharges at hyperpolarized levels (within membrane potential range of -60 to -85 mV). In all neurons, rhythmic patterns were superimposed on oscillations of membrane potential. They were characterized by a sudden shift of membrane potential, followed by a ramp-shaped phase of depolarization that preceded spike elicitation. Addition of TTX to the saline did not suppress NMDA-induced oscillations. Therefore rhythmic patterns were not driven by synaptic mechanisms but resulted from endogenous properties of cNTS neurons. 4. APs superimposed on NMDA-induced depolarizations presented the same characteristics as those elicited by positive current pulses. NMDA-elicited oscillations of membrane potential were eliminated by removing magnesium from the saline. Therefore oscillation generation was based primarily on the NMDA channel properties. 5. Intrinsic conductances of cNTS neurons interacted with NMDA-gated conductances to shape the depolarization waveform. Because removal of calcium from the saline suppressed endogenous oscillations, ICa currents were required for the expression of rhythmic activities. IKCa currents were involved in the repolarization phase of oscillations because apamin increased the duration of the oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)