title: Quantal size of catecholamine release from rat chromaffin cells is regulated by tonic activity of protein kinase A.
abstract: To address the roles of tonic activity of protein kinase A (PKA) in the regulation of exocytosis, we examined the effects of selective PKA inhibitors on catecholamine (CA) release from rat chromaffin cells in the absence of PKA activators. Myristoylated protein kinase inhibitor (myr-PKI) reduced the total amount of CA released from a single cell, whereas H-89 did not affect the total amount and frequency of CA release. Amperometric recording revealed that myr-PKI had only a small effect on the number of amperometric spikes per cell, but preferentially inhibited exocytotic events of large quantal size. The change in quantal size distribution was not associated with a reduction of cellular CA content, quantified by using HPLC. These results suggest that the tonic activity of PKA near the cell membrane regulates neurotransmitter release by modulating quantal size.
authors.affiliation: Department of Life Sciences (Biology), Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Koga
authors.forename: Masami
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides
chemical_list: D002352:Carrier Proteins; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010446:Peptide Fragments; D013449:Sulfonamides; C477818:myristoylated protein kinase A inhibitor amide 14-22; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium