cAMP-Mediated Stabilization of Fusion Pores in Cultured Rat Pituitary Lactotrophs
| العنوان: | cAMP-Mediated Stabilization of Fusion Pores in Cultured Rat Pituitary Lactotrophs |
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| المؤلفون: | Ana I. Calejo, Robert Zorec, Marek Kucka, Paula Gonçalves, Stanko S. Stojilkovic, Jernej Jorgačevski, Marko Kreft |
| المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| بيانات النشر: | Society for Neuroscience, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Patch-Clamp Techniques, Lactotrophs, Phosphodiesterase Inhibitors, Biology, Membrane Fusion, Exocytosis, Article, Membrane Potentials, Prolactin cell, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 1-Methyl-3-isobutylxanthine, Internal medicine, Cyclic AMP, medicine, Animals, Patch clamp, Rats, Wistar, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Forskolin, Bucladesine, Dose-Response Relationship, Drug, General Neuroscience, Vesicle, Colforsin, Lipid bilayer fusion, Prolactin, Rats, Endocrinology, chemistry, Pituitary Gland, Second messenger system, Biophysics, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Regulated exocytosis mediates the release of hormones and transmitters. The last step of this process is represented by the merger between the vesicle and the plasma membranes, and the formation of a fusion pore. Once formed, the initially stable and narrow fusion pore may reversibly widen (transient exocytosis) or fully open (full-fusion exocytosis). Exocytosis is typically triggered by an elevation in cytosolic calcium activity. However, other second messengers, such as cAMP, have been reported to modulate secretion. The way in which cAMP influences the transitions between different fusion pore states remains unclear. Here, hormone release studies show that prolactin release from isolated rat lactotrophs stimulated by forskolin, an activator of adenylyl cyclases, and by membrane-permeable cAMP analog (dbcAMP), exhibit a biphasic concentration dependency. Although at lower concentrations (2–10 μmforskolin and 2.5–5 mmdbcAMP) these agents stimulate prolactin release, an inhibition is measured at higher concentrations (50 μmforskolin and 10–15 mmdbcAMP). By using high-resolution capacitance (Cm) measurements, we recorded discrete increases in Cm, which represent elementary exocytic events. An elevation of cAMP leaves the frequency of full-fusion events unchanged while increasing the frequency of transient events. These exhibited a wider fusion pore as measured by increased fusion pore conductance and a prolonged fusion pore dwell time. The probability of observing rhythmic reopening of transient fusion pores was elevated by dbcAMP. In conclusion, cAMP-mediated stabilization of wide fusion pores prevents vesicles from proceeding to the full-fusion stage of exocytosis, which hinders vesicle content discharge at high cAMP concentrations. |
| تدمد: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.5351-12.2013 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::144c75ff8f4ddd2496d4bfc4c0e647e6 https://doi.org/10.1523/jneurosci.5351-12.2013 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....144c75ff8f4ddd2496d4bfc4c0e647e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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| DOI: | 10.1523/jneurosci.5351-12.2013 |