scholarly journals Pore dilation reconsidered

2015 ◽  
Vol 18 (11) ◽  
pp. 1534-1535 ◽  
Author(s):  
Bruce P Bean
Keyword(s):  
Pore Dilation

scholarly journals Synaptotagmin-Ca2+triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation

2006 ◽  
Vol 570 (2) ◽  
pp. 295-307 ◽  
Author(s):  
Chih-Tien Wang ◽  
Jihong Bai ◽  
Payne Y. Chang ◽  
Edwin R. Chapman ◽  
Meyer B. Jackson
Keyword(s):  
Pc12 Cells ◽  
Fusion Pore ◽  
Regulated Exocytosis ◽  
Pore Opening ◽  
Pore Dilation

scholarly journals Activity-Dependent Fusion Pore Dilation Mediated by a Dynamin I-Syndapin Pathway

2011 ◽  
Vol 100 (3) ◽  
pp. 408a
Author(s):  
Prattana Samasilp ◽  
Bryan Doreian ◽  
Shyue-An Chan ◽  
Corey Smith
Keyword(s):  
Fusion Pore ◽  
Pore Dilation ◽  
Dynamin I ◽  
Activity Dependent

scholarly journals Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

2013 ◽  
Vol 109 (7) ◽  
pp. 1704-1712 ◽  
Author(s):  
Michelino Puopolo ◽  
Alexander M. Binshtok ◽  
Gui-Lan Yao ◽  
Seog Bae Oh ◽  
Clifford J. Woolf ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Neuronal Cell ◽  
Reversal Potential ◽  
Dorsal Root Ganglion Neurons ◽  
C6 Glioma Cells ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Inward Currents ◽  
Pore Dilation ◽  
Ganglion Neurons

QX-314 ( N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/ PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry.

scholarly journals Cdc42 controls the dilation of the exocytotic fusion pore by regulating membrane tension

2014 ◽  
Vol 25 (20) ◽  
pp. 3195-3209 ◽  
Author(s):  
Marine Bretou ◽  
Ouardane Jouannot ◽  
Isabelle Fanget ◽  
Paolo Pierobon ◽  
Nathanaël Larochette ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Neuroendocrine Cells ◽  
Fusion Pore ◽  
Membrane Tension ◽  
Release Process ◽  
Vesicle Exocytosis ◽  
Pore Dilation ◽  
Pore Enlargement

Membrane fusion underlies multiple processes, including exocytosis of hormones and neurotransmitters. Membrane fusion starts with the formation of a narrow fusion pore. Radial expansion of this pore completes the process and allows fast release of secretory compounds, but this step remains poorly understood. Here we show that inhibiting the expression of the small GTPase Cdc42 or preventing its activation with a dominant negative Cdc42 construct in human neuroendocrine cells impaired the release process by compromising fusion pore enlargement. Consequently the mode of vesicle exocytosis was shifted from full-collapse fusion to kiss-and-run. Remarkably, Cdc42-knockdown cells showed reduced membrane tension, and the artificial increase of membrane tension restored fusion pore enlargement. Moreover, inhibiting the motor protein myosin II by blebbistatin decreased membrane tension, as well as fusion pore dilation. We conclude that membrane tension is the driving force for fusion pore dilation and that Cdc42 is a key regulator of this force.

scholarly journals Gating properties of the P2X2a and P2X2b receptor channels: Experiments and mathematical modeling

2012 ◽  
Vol 139 (5) ◽  
pp. 333-348 ◽  
Author(s):  
Anmar Khadra ◽  
Zonghe Yan ◽  
Claudio Coddou ◽  
Melanija Tomić ◽  
Arthur Sherman ◽  
...  
Keyword(s):  
Reversal Potential ◽  
Toggle Switch ◽  
Receptor Desensitization ◽  
Calcium Dependent ◽  
Terminal Domain ◽  
Total Conductance ◽  
Current Growth ◽  
Cell Recording ◽  
Pore Dilation ◽  
Splice Forms

Adenosine triphosphate (ATP)-gated P2X2 receptors exhibit two opposite activation-dependent changes, pore dilation and pore closing (desensitization), through a process that is incompletely understood. To address this issue and to clarify the roles of calcium and the C-terminal domain in gating, we combined biophysical and mathematical approaches using two splice forms of receptors: the full-size form (P2X2aR) and the shorter form missing 69 residues in the C-terminal domain (P2X2bR). Both receptors developed conductivity for N-methyl-d-glucamine within 2–6 s of ATP application. However, pore dilation was accompanied with a decrease rather than an increase in the total conductance, which temporally coincided with rapid and partial desensitization. During sustained agonist application, receptors continued to desensitize in calcium-independent and calcium-dependent modes. Calcium-independent desensitization was more pronounced in P2X2bR, and calcium-dependent desensitization was more pronounced in P2X2aR. In whole cell recording, we also observed use-dependent facilitation of desensitization of both receptors. Such behavior was accounted for by a 16-state Markov kinetic model describing ATP binding/unbinding and activation/desensitization. The model assumes that naive receptors open when two to three ATP molecules bind and undergo calcium-independent desensitization, causing a decrease in the total conductance, or pore dilation, causing a shift in the reversal potential. In calcium-containing media, receptor desensitization is facilitated and the use-dependent desensitization can be modeled by a calcium-dependent toggle switch. The experiments and the model together provide a rationale for the lack of sustained current growth in dilating P2X2Rs and show that receptors in the dilated state can also desensitize in the presence of calcium.

Pore dilation of neuronal P2X receptor channels

10.1038/7225 ◽  
1999 ◽  
Vol 2 (4) ◽  
pp. 315-321 ◽  
Author(s):  
C. Virginio ◽  
A. MacKenzie ◽  
F. A. Rassendren ◽  
R. A. North ◽  
A. Surprenant
Keyword(s):  
P2x Receptor ◽  
Pore Dilation

scholarly journals Synaptotagmin-7 links fusion-activated Ca2+ entry and fusion pore dilation

2014 ◽  
Vol 127 (24) ◽  
pp. 5218-5227 ◽  
Author(s):  
K. Neuland ◽  
N. Sharma ◽  
M. Frick
Keyword(s):  
Fusion Pore ◽  
Pore Dilation

scholarly journals The neuronal calcium sensor Synaptotagmin-1 and SNARE proteins cooperate to dilate fusion pores

2019 ◽  
Author(s):  
Zhenyong Wu ◽  
Nadiv Dharan ◽  
Sathish Thiyagarajan ◽  
Ben O’Shaughnessy ◽  
Erdem Karatekin
Keyword(s):  
Membrane Fusion ◽  
Snare Complex ◽  
Snare Proteins ◽  
Fusion Pore ◽  
Calcium Sensor ◽  
Fusion Reactions ◽  
Synaptotagmin 1 ◽  
Pore Opening ◽  
Pore Dilation ◽  
Fusion Pores

ABSTRACTAll membrane fusion reactions proceed through an initial fusion pore, including calcium-triggered vesicular release of neurotransmitters and hormones. Expansion of this small pore to release cargo molecules is energetically costly and regulated by cells, but the mechanisms are poorly understood. Here we show that the neuronal/exocytic calcium sensor Synaptotagmin-1 (Syt1) promotes expansion of fusion pores induced by SNARE proteins, beyond its established role in coupling calcium influx to fusion pore opening. Our results suggest that fusion pore dilation by Syt1 requires interactions with SNAREs, PI(4,5)P2, and calcium. Pore opening was abolished by a mutation of the tandem C2 domain (C2AB) hydrophobic loops of Syt1, suggesting that their calcium-induced insertion into the membrane is required for pore opening. We propose that loop insertion is also required for pore expansion, but through a distinct mechanism. Mathematical modelling suggests that membrane insertion re-orients the C2 domains bound to the SNARE complex, rotating the SNARE complex so as to exert force on the membranes in a mechanical lever action that increases the intermembrane distance. The increased membrane separation provokes pore dilation to offset a bending energy penalty. We conclude that Syt1 assumes a critical role in calcium-dependent fusion pore dilation during neurotransmitter and hormone release.SIGNIFICANCE STATEMENTMembrane fusion is a fundamental biological process, required for development, infection by enveloped viruses, fertilization, intracellular trafficking, and calcium-triggered release of neurotransmitters and hormones when cargo-laden vesicles fuse with the plasma membrane. All membrane fusion reactions proceed through an initial, nanometer-sized fusion pore which can flicker open-closed multiple times before expanding or resealing. Pore expansion is required for efficient cargo release, but underlying mechanisms are poorly understood. Using a combination of single-pore measurements and quantitative modeling, we suggest that a complex between the neuronal calcium sensor Synaptotagmin-1 and the SNARE proteins together act as a calcium-sensitive mechanical lever to force the membranes apart and enlarge the pore.

scholarly journals Allosteric regulation of the P2X4 receptor channel pore dilation

2014 ◽  
Vol 467 (4) ◽  
pp. 713-726 ◽  
Author(s):  
Hana Zemkova ◽  
Anmar Khadra ◽  
Milos B. Rokic ◽  
Vendula Tvrdonova ◽  
Arthur Sherman ◽  
...  
Keyword(s):  
Allosteric Regulation ◽  
Channel Pore ◽  
P2x4 Receptor ◽  
Pore Dilation ◽  
Receptor Channel
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