A choline-evoked [Ca2+](C) signal causes catecholamine release and hyperpolarization of chromaffin cells
Abstract
In bovine chromaffin cells fast-superfused with Krebs-HEPES solution containing 1 - 2 mM Ca2+, 5 s pulses of choline ( 1 - 10 mM), elicited catecholamine secretory responses that were only similar to10% of those evoked by ACh (0.01 - 0.1 mM). However, in high-Ca2+ solutions (10 - 20 mM) the size of the choline secretory responses approached those of ACh. The choline responses ( 10 mM choline in 20 mM Ca2+, 10Cho/20Ca(2+)) tended to decline upon repetitive pulsing, whereas those of ACh were well maintained. The confocal [Ca2+](c) increases evoked by 10Cho/20Ca(2+) were similar to those of ACh. Whereas 10Cho/20Ca(2+) caused mostly hyperpolarization of chromaffin cells, 0.1 ACh/20 Ca2+ caused first depolarization and then hyperpolarization; in regular solutions (2 mM Ca2+), the hyperpolarizing responses did not show up. In Xenopus oocytes injected with mRNA for bovine alpha7 nicotinic receptors (nAChRs), 10Cho/20 Ca2+ fully activated an inward current; in oocytes expressing alpha3beta4, however, the inward current elicited by choline amounted to only 4% of the size of alpha7 current. Our results suggest that choline activates the entry of Ca2+ through a7 nAChRs; this leads to a cytosolic concentration of calcium ([Ca2+](c)) rise that causes the activation of nearby Ca2+-dependent K+ channels and the hyperpolarization of the chromaffin cell. This response, which could be unmasked provided that cells were stimulated with high-Ca2+ solutions, may be the underlying mechanism through which choline exerts a modulatory effect on the electrical activity of the chromaffin cell and on neurotransmitter release at cholinergic synapses.
Más información
Título según WOS: | ID WOS:000222979200014 Not found in local WOS DB |
Título de la Revista: | FASEB JOURNAL |
Volumen: | 18 |
Número: | 10 |
Editorial: | Wiley |
Fecha de publicación: | 2004 |
Página de inicio: | 1468 |
Página final: | + |
DOI: |
10.1096/fj.04-1828fje |
Notas: | ISI |