Ion interaction at the pore of Lc-type Ca2+ channel is sufficient to mediate depolarization-induced exocytosis

Journal of Neurochemistry
Immanuel LernerDaphne Atlas

Abstract

The coupling of voltage-gated Ca2+ channel (VGCC) to exocytotic proteins suggests a regulatory function for the channel in depolarization-evoked exocytosis. To explore this possibility we have examined catecholamine secretion in PC12 and chromaffin cells. We found that replacing Ca2+ with La3+ or other lanthanide ions supported exocytosis in divalent ion-free solution. Cd2+, nifedipine, or verapamil inhibited depolarization-evoked secretion in La3+, indicating specific binding of La3+ at the pore of L-type VGCC, probably at the poly-glutamate (EEEE) locus. Lanthanide efficacy was stringently dependent on ionic radius with La3+>Ce3+>Pr3+, consistent with a size-selective binding interface of trivalent cations at the channel pore. La3+ inward currents were not detected and the highly sensitive La3+/fura-2 imaging assay (approximately 1 pm) detected no La3+ entry, cytosolic La3+ build-up, or alterations in cytosolic Ca2. These results provide strong evidence that occupancy of the pore of the channel by an impermeable cation leads to a conformational change that is transmitted to the exocytotic machinery upstream of intracellular cation build-up (intracellular Ca2+ concentration). Our model allows for a tight temporal and spatial c...Continue Reading

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Citations

Jan 7, 2014·Trends in Biochemical Sciences·Daphne Atlas
Jan 5, 2012·International Journal of Endocrinology·Niv BachnoffDaphne Atlas
Aug 14, 2012·Biochimica Et Biophysica Acta·Norbert Weiss, Gerald W Zamponi
Mar 8, 2011·Free Radical Biology & Medicine·Niv BachnoffDaphne Atlas
Nov 27, 2019·Acta Physiologica·José Moya-DíazFernando D Marengo
Nov 6, 2018·Frontiers in Cellular Neuroscience·Chao-Hua Huang, Tobias Moser
May 15, 2007·American Journal of Physiology. Cell Physiology·Jason I E Bruce, Austin C Elliott
Aug 29, 2018·Proceedings of the National Academy of Sciences of the United States of America·Evrim ServiliDaphne Atlas
Feb 25, 2015·Archives of Biochemistry and Biophysics·Elena C Gianulis, Andrei G Pakhomov
Dec 9, 2008·Biochemistry·Yamit HagaliliDaphne Atlas
Jul 16, 2008·Chemical Reviews·Christian AmatoreFrédéric Lemaître

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