Muscarinic receptors regulate two different calcium‐dependent non‐selective cation currents in rat prefrontal cortex

Pyramidal neurons of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) and a muscarinic‐induced slow afterdepolarization (sADP). We have shown previously that both of these ADPs are produced by the activation of calcium‐dependent non‐selective cation currents. In the present report we examine whether they represent two distinct currents. In most pyramidal neurons recorded with caesium gluconate‐based intracellular solution, a calcium spike is followed by a fast decaying inward aftercurrent (IfADP). The decay of IfADP is monoexponential with a time constant (τ) of ≈ 35 ms. Administration of carbachol (10–30 μm) increases the time constant of this decay by ≈ 80% and induces the appearance of a much slower inward aftercurrent (IsADP). IfADP recorded in control conditions and in the presence of carbachol increases linearly with membrane hyperpolarization. In contrast, the carbachol‐induced IsADP decreases with membrane hyperpolarization. When the sodium driving force across the cell membrane was reduced, IfADP was found to reverse at around −40 mV whereas IsADP remain inward over the same voltage range tested. Finally, bath administration of flufenamic acid (100 μm–1 mm) selectively blocks the carbachol‐induced IsADP without a significant effect on the amplitude of IfADP. These differences in the electrical and pharmacological properties of IfADP and IsADP suggest that they were mediated by two distinct non‐selective cation currents.