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 (I(fADP)). The decay of I(fADP) is monoexponential with a time constant (t) 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 (I(sADP)) I(fADP) recorded in control conditions and in the presence of carbachol increases linearly with membrane hyperpolarization. In contrast, the carbachol-induced I(sADP) decreases with membrane hyperpolarization. When the sodium driving force across the cell membrane was reduced, I(fADP) was found to reverse at around -40 mV whereas I(sADP) remain inward over the same voltage range tested. Finally, bath administration of flufenamic acid (100 μM - 1 mM) selectively blocks the carbachol-induced I(sADP) without a significant effect on the amplitude of I(fADP). These differences in the electrical and pharmacological properties of I(fADP) and I(sADP) suggest that they were mediated by two distinct non-selective cation currents.