Mobilization of calcium from intracellular stores, potentiation of neurotransmitter-induced calcium transients, and capacitative calcium entry by 4-aminopyridine

Citation
M. Grimaldi et al., Mobilization of calcium from intracellular stores, potentiation of neurotransmitter-induced calcium transients, and capacitative calcium entry by 4-aminopyridine, J NEUROSC, 21(9), 2001, pp. 3135-3143
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
9
Year of publication
2001
Pages
3135 - 3143
Database
ISI
SICI code
0270-6474(20010501)21:9<3135:MOCFIS>2.0.ZU;2-E
Abstract
In this study we analyzed the effect of 4-aminopyridine (4-AP) on free cyto solic calcium concentration ([Ca2+](i)) in basal conditions, after stimulat ion with neurotransmitters, and during capacitative calcium entry. Using fura-2 ratiometric calcium imaging, we found that 4-AP increased [Ca2 +](i) in type I astrocytes, neurons, and in skeletal muscle cells. The [Ca2 +](i) elevation induced by 4-AP was concentration-dependent and consisted o f two phases: the first was dependent on intracellular calcium mobilization , and the second was dependent on extracellular calcium influx. 4-AP also i ncreased the second messenger inositol trisphosphate in both neurons and as trocytes. In astrocytes, 4-AP treatment potentiated the sustained phase of the [Ca2+] (i) elevation induced by ATP and bradykinin. In addition, capacitative calc ium entry was potentiated severalfold by 4-AP, in astrocytes and muscle cel ls but not in neurons. These effects of 4-AP were completely and promptly r eversible. 4-AP blocked voltage-sensitive K+ currents in astrocytes. Howeve r, voltage-sensitive K+ channel blockers inhibiting these currents did not affect agonist-induced calcium transients or capacitative calcium entry, in dicating that 4-AP effects on [Ca2+](i) were not caused by the blockade of voltage-gated K+ channels. We conclude that 4-AP is able to affect calcium homeostasis at multiple lev els, from increasing basal [Ca2+](i) to potentiating capacitative calcium e ntry. The potentiation of capacitative calcium entry in astrocytes or muscl e cells may explain some of the therapeutic activities of 4-AP as a neurotr ansmission enhancer.