BIOPHYSICAL AND PHARMACOLOGICAL CHARACTERIZATION OF VOLTAGE-DEPENDENTCA2-ACCUMBENS( CHANNELS IN NEURONS ISOLATED FROM RAT NUCLEUS)

The nucleus accumbens (NA) has an integrative role in behavior and may mediate addictive and psychotherapeutic drug action. Whole cell recor ding techniques were used to characterize electrophysiologically and p harmacologically high- and low-threshold voltage-dependent Ca2+ curren ts in isolated NA neurons. High-threshold Ca2+ currents, which were fo und in all neurons studied and include both sustained and inactivating components, activated at potentials greater than -50 mV and reached m aximal activation at similar to 0 mV. In contrast, low-threshold Ca2currents activated at voltages greater than -64 mV with maximal activa tion occurring at -30 mV. These were observed in 42% of acutely isolat ed neurons. Further pharmacological characterization of high-threshold Ca2+ currents was attempted using nimodipine (Nim), omega-conotoxin-G VIA (omega-CgTx) and omega-agatoxin-IVA (omega Aga), which are thought to identify the L, N, and P/Q subtypes of Ca2+ currents, respectively . Nim (5-10 mu M) blocked 18%, omega CgTx (1-2 mu M) blocked 25%, and omega Aga (200 nM) blocked 17% of total Ca2+ current. Nim primarily bl ocked a sustained high-threshold Ca2+ current in a partially reversibl e manner. In contrast, omega CgTx irreversibly blocked both sustained and inactivating components. omega Aga irreversibly blocked only a sus tained component. In all three of these Ca2+ channel blockers, plus 5 mu M omega-conotoxin-MVIIC to eliminate a small unblocked Q-type Ca2current (7%), a toxin-resistant high-threshold Ca2+ current remained t hat was 32% of total Ca2+ current. This current inactivated much more rapidly than the other high-threshold Ca2+ currents, was depressed in 50 mu M Ni2+ and reached maximal activation 5-10 mV negative to the to xin-sensitive high-threshold Ca2+ currents. Thus NA neurons have multi ple types of high-threshold Ca2+ currents with a large component being the toxin-resistant ''R'' component.