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- W2317247256 abstract "Monoamine transporters take up neurotransmitters, but they also release neurotransmitters when challenged by abused drugs like amphetamine (AMPH) or MDMA (ecstasy). Transported substrates including transmitters and drugs are accompanied by excess positive charges that constitute an inward, depolarizing current. Previous research suggests that dopamine transporter (DAT) substrate-induced currents produce bursts of action potentials in dopaminergic neurons. Both pace-making and action potential bursting are mediated by L-type Ca2+ channels (CaV1.3) in several excitable cells, including some dopaminergic neurons, whereas N-type Ca2+ channels (CaV2.2) are mainly involved in neurotransmitter release. Here we test the hypothesis that monoamine transporters are electrically coupled to L-type Ca2+ channels. We express the serotonin transporter (SERT) in wt and CaV1.1-null myoblasts. After differentiation, wt myotubes, but not CaV1.1-null myotubes, release Ca2+ after 5HT or S(+)MDMA exposure, suggesting the participation of L-type Ca2+ channels. This effect was sensitive to fluoxetine but refractory to TTX, implicating SERT and excluding the participation of voltage-gated Na+ channels. Furthermore, co-expression of SERT & CaV1.3 in HEK cells supported Ca2+ signals, whereas SERT & CaV2.2 was unresponsive to 5HT or S(+)MDMA. Similarly, co-expression of DAT & CaV1.3 or DAT & CaV1.2 supported Ca2+ signals induced by S(+)AMPH or dopamine, whereas DAT & CaV2.2 expression was refractory to both agents even though S(+)AMPH has higher potency than dopamine. These data support the hypothesis that monoamine transporter substrate-induced current couples electrically to L-type Ca2+ channels but not to high-voltage-activated CaV2.2 channels. Support: NIH R01 DA033930" @default.
- W2317247256 created "2016-06-24" @default.
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- W2317247256 date "2015-01-01" @default.
- W2317247256 modified "2023-09-29" @default.
- W2317247256 title "Monoamine Transporters Produce Calcium Signals through L-Type Calcium Channel Activation" @default.
- W2317247256 doi "https://doi.org/10.1016/j.bpj.2014.11.2523" @default.
- W2317247256 hasPublicationYear "2015" @default.
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