Ionic dependence of a slow inward tail current in rat dorsal raphe neurones.

1. The mechanism underlying a large slow inward tail current was studied in serotonergic dorsal raphe (DR) neurones. The tail current is most easily observed under conditions of suppressed K+ channel outward currents and follows the activation of a calcium current. This current may underlie a slow after-depolarizing potential (ADP) which follows action potentials observed in acutely isolated DR neurones. 2. The after-hyperpolarizing potential (AHP) following action potentials which should reverse at EK (the reversal potential for potassium) becomes an ADP at less negative potentials than expected due to contamination by the slow inward tail current. 3. DR neurones were acutely isolated enzymatically; the ADP in current clamp and the tail current underlying it in voltage clamp were studied using the patch clamp method. When the external Na+ was replaced with TEA or choline the slow inward tail current was completely abolished. Blocking K+ channels from the inside of the cell membrane with 40 mM TEACl or large concentrations of internal Cs+ also blocked the slow inward tail current. 4. The tail current proved to be independent of calcium influx or intracellular calcium release as it was not affected by inorganic calcium channel blockers or caffeine. 5. The tail grew exponentially upon lengthening the depolarizing test pulse and appeared to reverse close to 0 mV indicating that the current was carried by a nonselective cation conductance. Removal of external Na+ and replacement with Li+ ions reversibly blocked the tail current by 77%. 6. The data rule out several mechanisms for the generation of the current, namely: a calcium-activated chloride conductance, a calcium-activated non-selective cation conductance, a Na(+)-Ca2+ exchange pump current or a sodium-activated K+ conductance. 7. The slow tail current may be explained by postulating an inward movement of Na+ through a channel which is blocked by high concentrations of external TEA and Li+ or internal Cs+ or 40 mM TEA.