Nitric oxide tonically depresses a voltage- and Ca-dependent outward current in hippocampal slices

Abstract

In whole-cell recordings from CAI neurons, net outward currents (at ca. −20 mV, from V H ca. −50 mV) were 40–50% depressed by sodium nitroprusside (100–500 μM) or l-arginine ( L-ARG; 50–200 μM), but not by D-arginine (100 μM). The NO synthase inhibitor N ω-nitro- l-arginine methyl ester ( l-NAME; 200 μM) restored the l-ARG-depressed current to ca. 80% of control. In naive cells, l-NAME increased outward currents by 45 ± 12.6 %; the enhanced currents were then reduced by adding L-ARG (200–400 μM). The NO-sensitive current is Ca-dependent, because l-NAME and l-ARG were ineffective in Mn/low Ca medium or when electrodes contained 2.2 mM EGTA. Since high voltage-activated Ca-currents were unaltered by l-NAME, we conclude that NO tonically enhances excitability in slices by depressing a voltage- and calcium-dependent ( I K(Ca)-type) outward current.