Muscarine increases cation conductance and decreases potassium conductance in rat locus coeruleus neurones.

1. Whole-cell patch-clamp recordings were made from rat locus coeruleus neurones in slices of brain tissue in vitro. Muscarine (30 microM) caused an inward current of about 100 pA in neurones voltage clamped at -60 mV. 2. In about 75% of cells, the current elicited by muscarine was independent of potential in the range -60 to -120 mV and had no associated conductance change. 3. In about 25% of cells, the current became smaller with hyperpolarization, was associated with a decreased conductance, and reversed polarity between -100 and -140 mV. The reversal potential changed with the logarithm of the extracellular potassium concentration. Barium and caesium blocked inward rectification and also prevented reversal of the muscarine current. 4. When potassium ions of the intracellular and extracellular solutions were replaced by caesium, the current evoked by muscarine became smaller with depolarization at reversed polarity at +9 mV. This current was associated with an increase in conductance, and was greatly reduced when the extracellular sodium concentration was reduced to 20 mM. 5. The results could be quantitatively accounted for by a model in which muscarine both increases a voltage-independent cation conductance and decreases the inward rectifier potassium conductance.