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Simultaneous Electrophysiological Recording and Calcium Imaging of Suprachiasmatic Nucleus Neurons
Published on: December 8, 2013
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Electrical coupling between the human serotonin transporter and voltage-gated Ca(2+) channels
Iwona Ruchala1, Vanessa Cabra1, Ernesto Solis1
1Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States.
Cell Calcium
|May 24, 2014
Summary
The human serotonin transporter (hSERT) interacts with calcium channels (CaV), specifically CaV1.3. This coupling modulates calcium signals in response to serotonin and ecstasy, impacting cellular excitability.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Monoamine transporters are crucial for neurotransmitter regulation and are targets of drugs like MDMA.
- Substrate-induced currents in monoamine transporters can affect cell excitability and calcium mobilization.
- The mechanism by which monoamine transporters influence calcium permeability remains unclear.
Purpose of the Study:
- To investigate the functional interaction between the human serotonin transporter (hSERT) and voltage-gated calcium channels (CaV).
- To elucidate the role of calcium channels in mediating the effects of hSERT substrates on cellular excitability.
Main Methods:
- Utilized an excitable muscle cell expression system engineered to express hSERT.
- Employed CaV1.1-null muscle cells to assess the necessity of specific calcium channels.
- Co-expressed hSERT with CaV1.3 and CaV2.2 channels in HEK293T cells to examine calcium transients.
Main Results:
- Serotonin (5HT) and S(+)MDMA depolarized hSERT-expressing muscle cells, activating excitation-contraction coupling.
- hSERT substrates failed to activate excitation-contraction coupling in CaV1.1-null cells, indicating a role for calcium channels.
- Co-expression of hSERT with CaV1.3, but not CaV2.2, in HEK293T cells resulted in serotonin- and S(+)MDMA-evoked calcium transients.
- Electrical coupling between hSERT and CaV1.3 occurred at physiological serotonin concentrations.
Conclusions:
- A novel functional interaction exists between the human serotonin transporter (hSERT) and the CaV1.3 calcium channel.
- This electrical coupling provides a mechanism for modulating calcium-dependent signals by both endogenous neurotransmitters and exogenous drugs like ecstasy.
- The findings highlight a new pathway through which monoamine transporter activity influences cellular excitability and calcium dynamics.
Keywords:
Calcium channelsCalcium imagingExcitabilityL-type calcium channelMonoamine transportersN-type calcium channelNeurotransmitter transportSkeletal muscleMore Related Videos
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