CaV3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons.
Neuropharmacology
; 135: 343-354, 2018 06.
Article
en En
| MEDLINE
| ID: mdl-29578032
ABSTRACT
Recent data have implicated voltage-gated calcium channels in the regulation of the excitability of neurons within the mesolimbic reward system. While the attention of most research has centered on high voltage L-type calcium channel activity, the presence and role of the low voltage-gated T-type calcium channel (T-channels) has not been well explored. Hence, we investigated T-channel properties in the neurons of the ventral tegmental area (VTA) utilizing wild-type (WT) rats and mice, CaV3.1 knock-out (KO) mice, and TH-eGFP knock-in (KI) rats in acute horizontal brain slices of adolescent animals. In voltage-clamp experiments, we first assessed T-channel activity in WT rats with characteristic properties of voltage-dependent activation and inactivation, as well as characteristic crisscrossing patterns of macroscopic current kinetics. T-current kinetics were similar in WT mice and WT rats but T-currents were abolished in CaV3.1 KO mice. In ensuing current-clamp experiments, we observed the presence of hyperpolarization-induced rebound burst firing in a subset of neurons in WT rats, as well as dopaminergic and non-dopaminergic neurons in TH-eGFP KI rats. Following the application of a pan-selective T-channel blocker TTA-P2, rebound bursting was significantly inhibited in all tested cells. In a behavioral assessment, the acute locomotor increase induced by a MK-801 (Dizocilpine) injection in WT mice was abolished in CaV3.1 KO mice, suggesting a tangible role for 3.1â¯T-type channels in drug response. We conclude that pharmacological targeting of CaV3.1 isoform of T-channels may be a novel approach for the treatment of disorders of mesolimbic reward system.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Potenciales de Acción
/
Área Tegmental Ventral
/
Canales de Calcio Tipo T
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos