A two-step model for acetylcholine control of exocytosis via nicotinic receptors.
The view that Ca(2+) entry through voltage-dependent Ca(2+) channels (VDCC) and through nicotinic receptors for acetylcholine (nAChRs) causes equal catecholamine release responses in chromaffin cells, was reinvestigated here using new protocols. We have made two-step experiments consisting in an ACh prepulse followed by a depolarizing pulse (DP). In voltage-clamped bovine chromaffin cells an ACh prepulse caused a slow-rate release but augmented 4.5-fold the much faster exocytotic response triggered by a subsequent depolarizing pulse (measured with capacitance and amperometry). If the ACh prepulse was given with mecamylamine or in low external Ca(2+), the secretion increase disappeared. This suggests a two-step model for the effects of ACh: (1) meager Ca(2+) entry through nAChRs mostly serves to keep loaded with vesicles the secretory machine; and (2) in this manner, the cell is prepared to respond with an explosive secretion of catecholamine upon depolarization and fast high Ca(2+) entry through VDCC.
Arnáiz-Cot
Juan J
JJ
Instituto "Teófilo Hernando" para la Investigación de Fármacos y del Envejecimiento (ITH), Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo, 4, 28029 Madrid, Spain.
de Diego
Antonio M G
AM
Hernández-Guijo
Jesús M
JM
Gandía
Luis
L
García
Antonio G
AG
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000378:metabolism*; D005071:Evoked Potentials; D005089:Exocytosis; D008954:Models, Biological; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000378:metabolism*
D015220:Calcium Channels; D002395:Catecholamines; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D002118:Calcium