Monoamine Transporters Produce Calcium Signals through L-Type Calcium Channel Activation
| Autor: | Louis J. De Felice, Krasnodara N. Cameron, Jose M. Eltit, Iwona Ruchala, Ernesto Solis |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0303 health sciences
medicine.medical_specialty Monoamine transporter biology Dopaminergic Biophysics Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Monoamine neurotransmitter Endocrinology chemistry Dopamine Internal medicine biology.protein medicine Neurotransmitter Amphetamine 030217 neurology & neurosurgery Serotonin transporter 030304 developmental biology Dopamine transporter medicine.drug |
| Zdroj: | Biophysical Journal. 108:462a-463a |
| ISSN: | 0006-3495 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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