Author/Editor		Calejo, AI; Jorgačevski, J; Silva, VS; Stenovec, M; Kreft, M; Goncalves, PP; Zorec, R
Title		Aluminium-induced changes of fusion pore properties attenuate prolactin secretion in rat pituitary lactotrophs
Type		članek
Source		Neuroscience
Vol. and No.		Letnik 201
Publication year		2012
Volume		str. 57-66
Language		eng
Abstract		Hormone secretion is mediated by Ca(2+)-regulated exocytosis. The key step of this process consists of the merger of the vesicle and the plasma membranes, leading to the formation of a fusion pore. This is an aqueous channel through which molecules stored in the vesicle lumen exit into the extracellular space on stimulation. Here we studied the effect of sub-lethal dose of aluminium on prolactin secretion in isolated rat pituitary lactotrophs with an enzyme immunoassay and by monitoring electrophysiologically the interaction of a single vesicle with the plasma membrane in real time, by monitoring membrane capacitance. After 24-h exposure to sub-lethal AlCl(3) (30 muM), the secretion of prolactin was reduced by 14+/-8% and 46+/-11% under spontaneous and K(+)-stimulated conditions, respectively. The frequency of unitary exocytotic events, recorded by the high-resolution patch-clamp monitoring of membrane capacitance, a parameter linearly related to the membrane area, under spontaneous and stimulated conditions, was decreased in aluminium-treated cells. Moreover, while the fusion pore dwell-time was increased in the presence of aluminium, the fusion pore conductance, a measure of fusion pore diameter, was reduced, both under spontaneous and stimulated conditions. These results suggest that sub-lethal aluminium concentrations reduce prolactin secretion downstream of the stimulus secretion coupling by decreasing the frequency of unitary exocytotic events and by stabilizing the fusion pore diameter to a value smaller than prolactin molecule, thus preventing its discharge into the extracellular space.
Descriptors		PITUITARY GLAND CELL MEMBRANE PERMEABILITY PROLACTIN ALUMINUM EXOCYTOSIS RATS, WISTAR CALCIUM POTASSIUM MEMBRANE FUSION IMMUNOENZYME TECHNIQUES ELECTRIC CONDUCTIVITY PATCH-CLAMP TECHNIQUES CELLS, CULTURED