Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
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 SOD1(G93A) (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 Ca(2+)-dependent K(+) current, and 53% in voltage-dependent K(+) current. Ca(2+) current was increased by 37%, but the ACh-evoked elevation of cytosolic Ca(2+) 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.
['Calvo-Gallardo|Enrique|E|', 'de Pascual|Ricardo|R|', 'Fernández-Morales|José-Carlos|JC|', 'Arranz-Tagarro|Juan-Alberto|JA|', 'Maroto|Marcos|M|', 'Nanclares|Carmen|C|', 'Gandía|Luis|L|', 'de Diego|Antonio M G|AM|', 'Padín|Juan-Fernando|JF|', 'García|Antonio G|AG|']
D000109:Acetylcholine D000200:Action Potentials D000367:Age Factors D000690:Amyotrophic Lateral Sclerosis D000818:Animals D002118:Calcium D020013:Calcium Signaling D002395:Catecholamines D019439:Chromaffin Cells D004195:Disease Models, Animal D005089:Exocytosis D006801:Humans D017136:Ion Transport D007700:Kinetics D008297:Male D008561:Membrane Fusion D008822:Mice, Transgenic D009043:Motor Activity D009046:Motor Neurons D009154:Mutation D011188:Potassium D011978:Receptors, Nicotinic D012964:Sodium D013482:Superoxide Dismutase D000072105:Superoxide Dismutase-1 D009435:Synaptic Transmission
fusion pore chromaffin cells amyotrophic lateral sclerosis exocytosis ion channel currents