Activation of the inositol 1,4,5-trisphosphate receptor by the calcium storage protein chromogranin A.
Secretory granules of neuroendocrine cells are inositol 1,4,5-trisphosphate (InsP(3))-sensitive Ca(2+) stores in which the Ca(2+) storage protein, chromogranin A (CGA), couples with InsP(3)-gated Ca(2+) channels (InsP(3)R) located in the granule membrane. The functional aspect of this coupling has been investigated via release studies and planar lipid bilayer experiments in the presence and absence of CGA. CGA drastically increased the release activity of the InsP(3)R by increasing the channel open probability by 9-fold and the mean open time by 12-fold. Our results show that CGA-coupled InsP(3)Rs are more sensitive to activation than uncoupled receptors. This modulation of InsP(3)R channel activity by CGA appears to be an essential component in the control of intracellular Ca(2+) concentration by secretory granules and may regulate the rate of vesicle fusion and exocytosis.
Thrower
Edwin C
EC
Department of Pharmacology, Yale University, New Haven, Connecticut 06520, USA. edwin.thrower@yale.edu
Park
Hee Yun
HY
So
Seung Ho
SH
Yoo
Seung Hyun
SH
Ehrlich
Barbara E
BE
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D002417:Cattle; D002531:Cerebellum / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D015640:Ion Channel Gating; D007700:Kinetics; D008051:Lipid Bilayers; D008081:Liposomes; D011510:Proteolipids / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*
D015220:Calcium Channels; D053379:Chromogranin A; D002864:Chromogranins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008051:Lipid Bilayers; D008081:Liposomes; D011510:Proteolipids; D018160:Receptors, Cytoplasmic and Nuclear; C020485:proteoliposomes; D006493:Heparin; D002118:Calcium