A concerted action of L- and T-type Ca2+ channels regulates locus coeruleus pacemaking
| Autor: | Niels Decher, Jochen Roeper, Lina A Matschke, Terrance P. Snutch, Wolfgang H. Oertel, Mirjam Bertoune, Susanne Rinné |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Patch-Clamp Techniques Calcium Channels L-Type Green Fluorescent Proteins Biophysics Action Potentials Tetrodotoxin In Vitro Techniques Biology Statistics Nonparametric Calcium Channels T-Type Mice Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Animals Channel blocker Patch clamp Molecular Biology Ion channel Neurons Mibefradil Afterhyperpolarization Cell Biology Calcium Channel Blockers Electric Stimulation Cell biology Mice Inbred C57BL Calcium Channel Agonists chemistry Locus coeruleus Locus Coeruleus Signal transduction Neuroscience Sodium Channel Blockers medicine.drug |
| Zdroj: | Molecular and Cellular Neuroscience. 68:293-302 |
| ISSN: | 1044-7431 |
| Popis: | Dysfunction of noradrenergic locus coeruleus (LC) neurons is involved in psychiatric and neurodegenerative diseases and is an early hallmark of Parkinson's disease (PD). The analysis of ion channels underlying the autonomous electrical activity of LC neurons, which is ultimately coupled to cell survival signaling pathways, can lead to a better understanding of the vulnerability of these neurons. In LC neurons somatodendritic Ca(2+) oscillations, mediated by L-type Ca(2+) channels, accompany spontaneous spiking and are linked to mitochondrial oxidant stress. However, the expression and functional implication of low-threshold activated T-type Ca(2+) channels in LC neurons were not yet studied. To this end we performed RT-PCR expression analysis in LC neurons. In addition, we utilized slice patch clamp recordings of in vitro brainstem slices in combination with L-type and T-type Ca(2+) channel blockers. We found the expression of a distinct set of L-type and T-type Ca(2+) channel subtypes mediating a pronounced low-threshold activated Ca(2+) current component. Analyzing spike trains, we revealed that neither L-type Ca(2+) channel nor T-type Ca(2+) channel blockade alone leads to a change in firing properties. In contrast, a combined application of antagonists significantly decreased the afterhyperpolarization amplitude, resulting in an increased firing frequency. Hence, we report the functional expression of T-type Ca(2+) channels in LC neurons and demonstrate their role in increasing the robustness of LC pacemaking by working in concert with Cav1 channels. |
| Databáze: | OpenAIRE |
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