Activation of GPCRs modulates quantal size in chromaffin cells through G(betagamma) and PKC.
Exocytosis proceeds by either full fusion or 'kiss-and-run' between vesicle and plasma membrane. Switching between these two modes permits the cell to regulate the kinetics and amount of secretion. Here we show that ATP receptor activation reduces secretion downstream from cytosolic Ca2+ elevation in rat adrenal chromaffin cells. This reduction is mediated by activation of a pertussis toxin-sensitive G(i/o) protein, leading to activation of G(betagamma) subunits, which promote the 'kiss-and-run' mode by reducing the total open time of the fusion pore during a vesicle fusion event. Furthermore, parallel activation of the muscarinic acetylcholine receptor removes the inhibitory effects of ATP on secretion. This is mediated by a G(q) pathway through protein kinase C activation. The inhibitory effects of ATP and its reversal by protein kinase C activation are also shared by opioids and somatostatin. Thus, a variety of G protein pathways exist to modulate Ca2+-evoked secretion at specific steps in fusion pore formation.
Chen
Xiao-Ke
XK
Institute of Neuroscience, Shanghai Institutes for Biological Sciences and Graduate School, Chinese Academy of Sciences, Shanghai 200031, China.
Wang
Lie-Cheng
LC
Zhou
Yang
Y
Cai
Qian
Q
Prakriya
Murali
M
Duan
Kai-Lai
KL
Sheng
Zu-Hang
ZH
Lingle
Christopher
C
Zhou
Zhuan
Z
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D034281:Dynamins / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D004563:Electrochemistry / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism* / Q000494:pharmacology; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009116:Muscarine / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D037342:Pertussis Toxin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013004:Somatostatin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000701:Analgesics, Opioid; D004791:Enzyme Inhibitors; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D007476:Ionophores; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D013873:Thionucleotides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D013004:Somatostatin; D015759:Ionomycin; D011189:Potassium Chloride; D009116:Muscarine; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D011494:Protein Kinases; D011493:Protein Kinase C; D034281:Dynamins; D002118:Calcium; C008501:2-methylthio-ATP