Haj-Dahmane, Samir and Rodrigo Andrade. Calcium-activated cation nonselective current contributes to the fast afterdepolarization in rat prefrontal cortex neurons. J. Neurophysiol. 78: 1983–1989, 1997. Pyramidal cells of layer V in rat prefrontal cortex display a prominent fast afterdepolarization (fADP) following an action potential. This ADP is blocked by replacing extracellular calcium with magnesium, by the application of the calcium-channel blocker cadmium, and by buffering intracellular calcium at near physiological levels. Thus this fast ADP appears mediated by a calcium-activated current. A prominent ADP is also observed following a calcium spike recorded in the presence of tetrodotoxin. The current underlying this ADP was recorded using a hybrid current-voltage protocol. A strong ADP could be observed in the presence of potassium channel blockers as well as at E_Cl. Furthermore, the current underlying the ADP increased with hyperpolarization in the subthreshold range and displayed an extrapolated reversal potential near +30 mV. Reducing the ratio of extracellular to intracellular sodium inhibited the current underlying the ADP and caused a hyperpolarizing shift in its reversal potential. We conclude that these cells express a calcium-activated cation nonselective current whose activation contributes to the generation of the fADP. This current could play an important role in determining the firing properties of pyramidal cells in cortex.