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Low-threshold L-type calcium channels in rat dopamine neurons
P Durante1, C G Cardenas, J A Whittaker
1Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Journal of Neurophysiology
|December 3, 2003
Summary
Dopaminergic neurons in the substantia nigra pars compacta utilize L-type calcium channels (Ca(2+)) more than N- or P-type channels for spontaneous firing. These channels activate at more negative potentials, explaining drug effects.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) exhibit spontaneous oscillatory potentials and rhythmic firing.
- Calcium (Ca(2+)) channels play a crucial role in neuronal excitability and neurotransmitter release.
Purpose of the Study:
- To investigate the subtypes of Ca(2+) channels expressed by SNc DA neurons.
- To determine the contribution of different Ca(2+) channel subtypes to neuronal activity.
- To compare the activation properties of Ca(2+) channels in DA neurons with those in other neuronal types.
Main Methods:
- Whole-cell patch-clamp recordings were employed to measure Ca(2+) channel currents.
- Selective channel blockers, including Nimodipine (L-type), omega-conotoxin GVIA (N-type), and omega-agatoxin IVA (P/Q-type), were used to differentiate channel contributions.
Main Results:
- L-, N-, and P-type Ca(2+) channels were identified in SNc DA neurons, contributing 27%, 36%, and 37% of the peak current, respectively.
- L-type Ca(2+) channels were preferentially activated at more negative potentials compared to N- and P-type channels.
- Ca(2+) channels in DA neurons showed a more negative activation voltage range than those in rat dorsal root ganglion cells.
Conclusions:
- The preferential activation of L-type Ca(2+) channels at negative potentials explains why L-channel antagonists, but not N-channel antagonists, block spontaneous firing in DA neurons.
- Pharmacologically similar Ca(2+) channels can exhibit distinct activation thresholds in different neuronal populations.
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