The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 635-647
Copyright ©1998 The American Physiological Society

Biophysical and Pharmacological Characterization of Voltage-Dependent Ca²⁺ Channels in Neurons Isolated From Rat Nucleus Accumbens

Dennis Churchill and Brian A. Macvicar

Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta T2N 4N1, Canada

Churchill, Dennis and Brian A. MacVicar. Biophysical and pharmacological characterization of voltage-dependent Ca²⁺ channels in neurons isolated from rat nucleus accumbens. J. Neurophysiol. 79: 635-647, 1998. The nucleus accumbens (NA) has an integrative role in behavior and may mediate addictive and psychotherapeutic drug action. Whole cell recording techniques were used to characterize electrophysiologically and pharmacologically high- and low-threshold voltage-dependent Ca²⁺ currents in isolated NA neurons. High-threshold Ca²⁺ currents, which were found in all neurons studied and include both sustained and inactivating components, activated at potentials greater than 50 mV and reached maximal activation at ~0 mV. In contrast, low-threshold Ca²⁺ currents activated at voltages greater than 64 mV with maximal activation occurring at 30 mV. These were observed in 42% of acutely isolated neurons. Further pharmacological characterization of high-threshold Ca²⁺ currents was attempted using nimodipine (Nim), -conotoxin-GVIA (-CgTx) and -agatoxin-IVA (Aga), which are thought to identify the L, N, and P/Q subtypes of Ca²⁺ currents, respectively. Nim (5-10 µM) blocked 18%, CgTx (1-2 µM) blocked 25%, and Aga (200 nM) blocked 17% of total Ca²⁺ current. Nim primarily blocked a sustained high-threshold Ca²⁺ current in a partially reversible manner. In contrast, CgTx irreversibly blocked both sustained and inactivating components. Aga irreversibly blocked only a sustained component. In all three of these Ca²⁺ channel blockers, plus 5 µM -conotoxin-MVIIC to eliminate a small unblocked Q-type Ca²⁺ current (7%), a toxin-resistant high-threshold Ca²⁺ current remained that was 32% of total Ca²⁺ current. This current inactivated much more rapidly than the other high-threshold Ca²⁺ currents, was depressed in 50 µM Ni²⁺ and reached maximal activation 5-10 mV negative to the toxin-sensitive high-threshold Ca²⁺ currents. Thus NA neurons have multiple types of high-threshold Ca²⁺ currents with a large component being the toxin-resistant "R" component.

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