Nitric oxide tonically depresses a voltage- and Ca-dependent outward current in hippocampal slices.
In whole-cell recordings from CA1 neurons, net outward currents (at ca. -20 mV, from VH ca. -50 mV) were 40-50% depressed by sodium nitroprusside (100-500 microM) or L-arginine (L-ARG; 50-200 microM), but not by D-arginine (100 microM). The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 200 microM) 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 microM). 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 (IK(Ca)-type) outward current.
Erdemli
G
G
Anaesthesia Research Department, McGill University, Montréal, Canada.
Krnjević
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D003864:Depression, Chemical; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester