Calcium Dynamics
-
Upload
kibo-dudley -
Category
Documents
-
view
28 -
download
0
description
Transcript of Calcium Dynamics
![Page 1: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/1.jpg)
Calcium Dynamics
Basic reference: Keener and Sneyd, Mathematical Physiology
![Page 2: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/2.jpg)
• In the previous talk we concentrated on Na+ and K+, as those are the ions that are most important for the control of cell volume and the membrane potential.
• But Ca2+ plays an equally important role in practically every cell type.
• Ca2+ controls secretion, cell movement, muscular contraction, cell differentiation, ciliary beating, and so on.
• Important in both excitable and non-excitable cells.
Calcium is a vital second messenger
![Page 3: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/3.jpg)
Calcium in muscle: I
![Page 4: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/4.jpg)
Calcium in muscle: II
![Page 5: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/5.jpg)
Calcium in phototransduction
![Page 6: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/6.jpg)
Calcium in phototransduction
![Page 7: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/7.jpg)
Calcium in taste receptors
![Page 8: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/8.jpg)
Calcium and synapses: I
![Page 9: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/9.jpg)
Calcium and synapses: II
![Page 10: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/10.jpg)
A: Hepatocytes
B: Rat parotid gland
C: Gonadotropes
D: Hamster eggs (post-fertilization)
E, F: Insulinoma cells
Typical Calcium Oscillations
![Page 11: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/11.jpg)
Inward flux of calcium through voltage-gated calcium channels. Dependent on fluctuations of the membrane potential.
Often seen in electrically excitable cells such as neurosecretory cells
Not dependent on membrane potential. Oscillations arise from recycling of calcium to and from internal stores (ER and mitochondria)
Ryanodinereceptors
IP3 receptors
Muscle cells and many neurons
Electrically non-excitable cells. Smooth muscle
Three principal mechanisms
![Page 12: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/12.jpg)
Summary of calcium homeostasis
ER
Mitochondria
Ca2+
Ca2+
Ca2+-B(buffering)serca
IPR
RyR
PM pumps
ICa
leak
![Page 13: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/13.jpg)
Cardiac cells - EC Coupling
ER
Ca2+
Ca2+
serca
RyR
NCX
L-type channel(voltage gated)
Na+
Na+
![Page 14: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/14.jpg)
Calcium excitability• Both IPR and RyR release calcium in an excitable manner. They both respond to a calcium challenge by the release of even more calcium.
• The precise mechanisms are not known for sure (although detailed models can be constructed).
• An IPR behaves like a Na+ channel (in some ways). In response to an increase in [Ca2+] it first activates quickly, and then inactivates slowly, resulting in the short-term release of a large amount of calcium.
• A lot of attention has been focused on IPR and RyR. Less on pumping. But the dynamics of pumping is equally important.
![Page 15: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/15.jpg)
IP3 Receptor pathway
![Page 16: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/16.jpg)
Ryanodine Receptor pathway
![Page 17: Calcium Dynamics](https://reader036.fdocuments.us/reader036/viewer/2022062421/56812a71550346895d8df4a2/html5/thumbnails/17.jpg)
Generic modellingSet up a typical reaction diffusion equation for calcium:
€
∂c∂t
= D∇ 2c + (JIPR + JRyR − Jserca ) + (Jleak − JPM + JI ) + (Jm,out − Jm,in ) − k1c(bt −b) + k2b
ER fluxes PM fluxesmitochondrial
fluxesbuffering
• This reaction-diffusion equation is coupled to a system of o.d.e.s (or p.d.e.s), describing the various receptor states, IP3, the reaction and diffusion of the buffers, calcium inside the ER or mitochondria, or any other important species.
• The specifics of the coupled o.d.e.s depend on which particular model is being used.
• Sometimes the PM fluxes appear only as boundary conditions, sometimes not, depending on the exact assumptions made about the spatial properties of the cell.
• In general the buffering flux is a sum of terms, describing buffering by multiple diffusing buffers.
Total buffer