A novel voltage-dependent cation current in rat neocortical neurones.

1. Using the whole-cell configuration of the patch-clamp technique, an unexpected voltage-dependent cation current (Icat) was recorded from acutely isolated rat neocortical neurones, the Na+, K+ and Ca2+ currents of which were pharmacologically suppressed. 2. Icat was activated at potentials more positive than -45 mV, displayed outward rectification, and deactivated with a slow voltage-dependent time course causing prominent inward tail currents. 3. Activation of Icat was not dependent on Ca2+ influx or increases in cytosolic Ca2+, since it was not abolished by inorganic Ca2+ channel blockers or by internal Ca2+ chelators. 4. Icat was reduced by tetraethylammonium at high concentrations, but not by 4-amino-pyridine, and proved to be insensitive to cation channel blockers such as Cs+, amiloride or gadolinium. 5. Ion substitution experiments revealed that the channel producing Icat was permeable to a number of monovalent cations, including K+, Cs+, Na+ and choline+, but not to the Cl-anion. 6. The features of Icat suggest that, in electrically active neurones, it should play a role in both the initial repolarization of membrane potential after strong depolarization and the generation of depolarizing after-potential.