A NOVEL VOLTAGE-DEPENDENT CATION CURRENT IN RAT NEOCORTICAL NEURONS

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