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Acute reversible SERCA blockade facilitates or blocks exocytosis, respectively in mouse or bovine chromaffin cells.

Authors
  • Martínez-Ramírez, Carmen1, 2, 3
  • Gil-Gómez, Irene1, 2, 3
  • G de Diego, Antonio M4, 5, 6, 7, 8
  • García, Antonio G1, 2, 3, 9, 10
  • 1 Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain. , (Spain)
  • 2 Departamento de Farmacología, Universidad Autónoma de Madrid, Madrid, Spain. , (Spain)
  • 3 Fundación Teófilo Hernando, Parque científico de Madrid, Madrid, Spain. , (Spain)
  • 4 Instituto Teófilo Hernando, Universidad Autónoma de Madrid, Madrid, Spain. [email protected] , (Spain)
  • 5 Departamento de Farmacología, Universidad Autónoma de Madrid, Madrid, Spain. [email protected] , (Spain)
  • 6 Fundación Teófilo Hernando, Parque científico de Madrid, Madrid, Spain. [email protected] , (Spain)
  • 7 Instituto de Investigación Sanitaria del Hospital de La Princesa, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. [email protected] , (Spain)
  • 8 DNS Neuroscience, Instituto Teófilo Hernando, Department of Pharmacology, Universidad Autónoma de Madrid, Madrid, Spain. [email protected] , (Spain)
  • 9 Instituto de Investigación Sanitaria del Hospital de La Princesa, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. , (Spain)
  • 10 DNS Neuroscience, Instituto Teófilo Hernando, Department of Pharmacology, Universidad Autónoma de Madrid, Madrid, Spain. , (Spain)
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Oct 27, 2020
Identifiers
DOI: 10.1007/s00424-020-02483-1
PMID: 33108514
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pre-blockade of the sarco-endoplasmic reticulum (ER) calcium ATPase (SERCA) with irreversible thapsigargin depresses exocytosis in adrenal bovine chromaffin cells (BCCs). Distinct expression of voltage-dependent Ca2+-channel subtypes and of the Ca2+-induced Ca2+ release (CICR) mechanism in BCCs versus mouse chromaffin cells (MCCs) has been described. We present a parallel study on the effects of the acute SERCA blockade with reversible cyclopizonic acid (CPA), to repeated pulsing with acetylcholine (ACh) at short (15 s) and long intervals (60 s) at 37 °C, allowing the monitoring of the initial size of a ready-release vesicle pool (RRP) and its depletion and recovery in subsequent stimuli. We found (i) strong depression of exocytosis upon ACh pulsing at 15-s intervals and slower depression at 60-s intervals in both cell types; (ii) facilitation of exocytosis upon acute SERCA inhibition, with back to depression upon CPA washout in MCCs; (iii) blockade of exocytosis upon acute SERCA inhibition and pronounced rebound of exocytosis upon CPA washout in BCCs; (iv) basal [Ca2+]c elevation upon stimulation with ACh at short intervals (but not at long intervals) in both cell types; and (v) augmentation of basal [Ca2+]c and inhibition of peak [Ca2+]c amplitude upon CPA treatment in both cell types, with milder effects upon stimulation at 60-s intervals. These results are compatible with the view that while in MCCs the uptake of Ca2+ via SERCA contributes to the mitigation of physiological ACh triggered secretion, in BCCs the uptake of Ca2+ into the ER facilitates such responses likely potentiating a Ca2+-induced Ca2+ release mechanism. These drastic differences in the regulation of ACh-triggered secretion at 37 °C may help to understand different patterns of the regulation of exocytosis by the circulation of Ca2+ at a functional ER Ca2+ store.

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