Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis
EntityUAM. Departamento de Farmacología
PublisherAmerican Physiological Society
10.1152/ajpcell.00272.2014American journal of physiology. Cell physiology 308.1 (2015): C1-C19
ISSN0363-6143 (print); 1522-1563 (on line)
Funded byThis work was funded by: (1) SAF-2010-21795, MINECO; (2) SAF-2010-792 18837, MINECO; (3) CABICYC, UAM/Bioibérica; (4) Fundación Teófilo 793 Hernando, Madrid, Spain
ProjectGobierno de España. SAF-2010-21795; Gobierno de España. SAF-2010-792 18837,
SubjectsAmyotrophic lateral sclerosis; Fusion pore; Chromaffin cells; Exocytosis; Ion channel currents; Medicina
Altered synaptic transmission with excess glutamate release has been implicated in the loss of motoneurons occurring in amyotrophic lateral sclerosis (ALS). Hyperexcitability or hypoexcitability of motoneurons from mice carrying the ALS mutation SOD1G93A (mSOD1) has also been reported. Here we have investigated the excitability, the ion currents, and the kinetics of the exocytotic fusion pore in chromaffin cells from postnatal day 90 to postnatal day 130 mSOD1 mice, when motor deficits are already established. With respect to wild-type (WT), mSOD1 chromaffin cells had a decrease in the following parameters: 95% in spontaneous action potentials, 70% in nicotinic current for acetylcholine (ACh), 35% in Na+ current, 40% in Ca2+-dependent K+ current, and 53% in voltage-dependent K+ current. Ca2+ current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca2+ was unchanged. Single exocytotic spike events triggered by ACh had the following differences (mSOD1 vs. WT): 36% lower rise rate, 60% higher decay time, 51% higher half-width, 13% lower amplitude, and 61% higher quantal size. The expression of the α3-subtype of nicotinic receptors and proteins of the exocytotic machinery was unchanged in the brain and adrenal medulla of mSOD1, with respect to WT mice. A slower fusion pore opening, expansion, and closure are likely linked to the pronounced reduction in cell excitability and in the ion currents driving action potentials in mSOD1, compared with WT chromaffin cells.
Google Scholar:Calvo-Gallardo, Enrique - de Pascual, Ricardo - Fernández Morales, José Carlos - Arranz-Tagarro, Juan Alberto - Maroto, Marcos - Nanclares, Carmen - Gandía Juan, Luis - de Diego, Antonio M G - Padín, Juan Fernando - García, Antonio G.
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