Biology – Quantitative Biology – Quantitative Methods
Scientific paper
2009-08-19
Biochem Biophys Res Commun 389, 461-465 (2009)
Biology
Quantitative Biology
Quantitative Methods
16 pages, 9 figures; an abridged version submitted for publication
Scientific paper
10.1016/j.bbrc.2009.08.166
We present a stochastic computational model to study the mechanism of signalling between a source and a target ionic transporter, both localized on the plasma membrane (PM) and in intracellular nanometre-scale subplasmalemmal signalling compartments comprising the PM, the sarcoplasmic reticulum (SR), Ca2+ and Na+ transporters, and the intervening cytosol. We refer to these compartments, sometimes called junctions, as cytoplasmic nanospaces or nanodomains. In the chain of events leading to Ca2+ influx for SR reloading during asynchronous Ca2+ waves in vascular smooth muscle (VSM), the physical and functional link between non-selective cation channels (NSCC) and Na+/Ca2+ exchangers (NCX) needs to be elucidated in view of two recent findings: the identification of the transient receptor potential canonical channel 6 (TRPC6) as a crucial NSCC in VSM cells and the observation of localized cytosolic [Na+] transients following purinergic stimulation of these cells. Having previously helped clarify the Ca2+ signalling step between NCX and SERCA behind SR Ca2+ refilling, this quantitative approach now allows us to model the upstream linkage of NSCC and NCX. We have implemented a random walk (RW) Monte Carlo (MC) model with simulations mimicking a Na+ diffusion process originating at the NSCC within PM-SR junctions. The model calculates the average [Na+] in the nanospace and also produces [Na+] profiles as a function of distance from the Na+ source. Our results highlight the necessity of a strategic juxtaposition of the relevant signalling channels as well as other physical structures within the nanospaces to permit adequate [Na+] build-up to provoke NCX reversal and Ca2+ influx to refill the SR.
Breemen Cornelis van
Fameli Nicola
Kuo Kuo-Hsing
No associations
LandOfFree
A model for the generation of localized transient Na+ elevations in vascular smooth muscle does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.
If you have personal experience with A model for the generation of localized transient Na+ elevations in vascular smooth muscle, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and A model for the generation of localized transient Na+ elevations in vascular smooth muscle will most certainly appreciate the feedback.
Profile ID: LFWR-SCP-O-525589