Electrical coupling between the human Serotonin Transporter and Voltage-Gated Ca2+ Channels
| Autor: | Vanessa Cabra, Louis J. De Felice, Iwona Ruchala, Jose M. Eltit, Richard A. Glennon, Ernesto Solis |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Serotonin
Cell Membrane Permeability Physiology N-Methyl-3 4-methylenedioxyamphetamine Biology Article Myoblasts chemistry.chemical_compound Mice Animals Humans Calcium Signaling Transgenes Neurotransmitter Muscle Skeletal Molecular Biology 5-HT receptor Excitation Contraction Coupling Serotonin Plasma Membrane Transport Proteins Voltage-dependent calcium channel Voltage-gated ion channel Cell Biology Monoamine neurotransmitter HEK293 Cells chemistry Biochemistry Neuromuscular Depolarizing Agents Biophysics Calcium Channels Neurotransmitter transport |
| Popis: | Monoamine transporters have been implicated in dopamine or serotonin release in response to abused drugs such as methamphetamine or ecstasy (MDMA). In addition, monoamine transporters show substrate-induced inward currents that may modulate excitability and Ca(2+) mobilization, which could also contribute to neurotransmitter release. How monoamine transporters modulate Ca(2+) permeability is currently unknown. We investigate the functional interaction between the human serotonin transporter (hSERT) and voltage-gated Ca(2+) channels (CaV). We introduce an excitable expression system consisting of cultured muscle cells genetically engineered to express hSERT. Both 5HT and S(+)MDMA depolarize these cells and activate the excitation-contraction (EC)-coupling mechanism. However, hSERT substrates fail to activate EC-coupling in CaV1.1-null muscle cells, thus implicating Ca(2+) channels. CaV1.3 and CaV2.2 channels are natively expressed in neurons. When these channels are co-expressed with hSERT in HEK293T cells, only cells expressing the lower-threshold L-type CaV1.3 channel show Ca(2+) transients evoked by 5HT or S(+)MDMA. In addition, the electrical coupling between hSERT and CaV1.3 takes place at physiological 5HT concentrations. The electrical coupling between monoamine neurotransmitter transporters and Ca(2+) channels such as CaV1.3 is a novel mechanism by which endogenous substrates (neurotransmitters) or exogenous substrates (like ecstasy) could modulate Ca(2+)-driven signals in excitable cells. |
| Databáze: | OpenAIRE |
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