Whole-cell recordings were made from neurons of the rat locus coeruleus in a tissue slice removed from rat brain. Substance P caused an inward current in cells voltage-clamped at -60 mV. The effect of substance P was concentration-dependent (30nM-3 μM) and was mimicked by similar concentrations of substance K and neuromedin K. The inward current resulted predominately from an increase in membrane cation conductance; in potassium-free solutions it reversed polarity at about 12 mV. Substance P also reduced the conductance of an inwardly rectifying potassium current; this action was studied with low external sodium concentration. p It is concluded that substance P excites rat locus coeruleus neurons by activating an intracellular transduction pathway leading to both cation conductance increase and potassium conductance decrease.
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