PKC Enhances the Capacity for Secretion by Rapidly Recruiting Covert Voltage-Gated Ca2+Channels to the Membrane
| Autor: | Christopher J. Groten, Neil S. Magoski |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Recruitment
Neurophysiological medicine.medical_specialty Patch-Clamp Techniques Biology Exocytosis immune system diseases Internal medicine Aplysia medicine Animals Secretion Cytoskeleton neoplasms Protein Kinase C Protein kinase C Neurons Voltage-gated ion channel General Neuroscience Cell Membrane Articles Peptide secretion biology.organism_classification Actins Mitochondria Cell biology Enzyme Activation Endocrinology Tetradecanoylphorbol Acetate Latrunculin Calcium Calcium Channels |
| Zdroj: | The Journal of Neuroscience. 35:2747-2765 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3581-14.2015 |
| Popis: | It is unknown whether neurons can dynamically control the capacity for secretion by promptly changing the number of plasma membrane voltage-gated Ca2+channels. To address this, we studied peptide release from the bag cell neurons ofAplysia californica, which initiate reproduction by secreting hormone during an afterdischarge. This burst engages protein kinase C (PKC) to trigger the insertion of a covert Ca2+channel, Apl Cav2, alongside a basal channel, Apl Cav1. The significance of Apl Cav2 recruitment to secretion remains undetermined; therefore, we used capacitance tracking to assay secretion, along with Ca2+imaging and Ca2+current measurements, from cultured bag cell neurons under whole-cell voltage-clamp. Activating PKC with the phorbol ester, PMA, enhanced Ca2+entry, and potentiated stimulus-evoked secretion. This relied on channel insertion, as it was occluded by preventing Apl Cav2 engagement with prior whole-cell dialysis or the cytoskeletal toxin, latrunculin B. Channel insertion reduced the stimulus duration and/or frequency required to initiate secretion and strengthened excitation-secretion coupling, indicating that Apl Cav2 accesses peptide release more readily than Apl Cav1. The coupling of Apl Cav2 to secretion also changed with behavioral state, as Apl Cav2 failed to evoke secretion in silent neurons from reproductively inactive animals. Finally, PKC also acted secondarily to enhance prolonged exocytosis triggered by mitochondrial Ca2+release. Collectively, our results suggest that bag cell neurons dynamically elevate Ca2+channel abundance in the membrane to ensure adequate secretion during the afterdischarge. |
| Databáze: | OpenAIRE |
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