Low-threshold L-type calcium channels in rat dopamine neurons.
Ca(2+) channel subtypes expressed by dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) were studied using whole cell patch-clamp recordings and blockers selective for different channel types (L, N, and P/Q). Nimodipine (Nim, 2 microM), omega-conotoxin GVIA (Ctx, 1 microM), or omega-agatoxin IVA (Atx, 50 nM) blocked 27, 36, and 37% of peak whole cell Ca(2+) channel current, respectively, indicating the presence of L-, N-, and P-type channels. Nim blocked approximately twice as much Ca(2+) channel current near activation threshold compared with Ctx or Atx, suggesting that small depolarizations preferentially opened L-type versus N- or P-type Ca(2+) channels. N- and L-channels in DA neurons opened over a significantly more negative voltage range than those in rat dorsal root ganglion cells, recorded from using identical conditions. These data provide an explanation as to why Ca(2+)-dependent spontaneous oscillatory potentials and rhythmic firing in DA neurons are blocked by L-channel but not N-channel antagonists and suggest that pharmacologically similar Ca(2+) channels may exhibit different thresholds for activation in different types of neurons.
Durante
P
P
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Cardenas
C G
CG
Whittaker
J A
JA
Kitai
S T
ST
Scroggs
R S
RS
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology; D020865:Calcium Channels, P-Type / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020867:omega-Agatoxin IVA; D009553:Nimodipine; D020866:omega-Conotoxin GVIA; D004298:Dopamine