spatial buffering of k+ in relation to spreading depression models tony gardner-medwin physiology...

11
Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

Upload: lesley-francis

Post on 05-Jan-2016

217 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

Spatial Buffering of K+ in Relation to Spreading Depression Models

Tony Gardner-Medwin

Physiology (NPP), University College London

Page 2: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M, COLES and TSACOPOULOS

Brain Research, 209 (1981) 452-457

Page 3: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

K+ release from photoreceptors and uptake into glia in bee eye

[K+]o

[K+]i

(mM)

[K+]i

G-M, COLES and TSACOPOULOS

Brain Research, 209 (1981) 452-457

Page 4: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

Spatial Buffer Mechanism: passive removal & transfer of e-c K+ through (mainly) astrocyte membranes & cytoplasm

Transfer Cells: (K+-selective)

Flux driven by a chemical gradient

Computational analysis

Flux driven by an electrical gradient

G-M (1983)J Physiol 335 393-426

Conclusions: SB flux ≈ 5x diffusion fluxSpace constant ≈ 0.2 mm (rat brain), 0.03 mm (frog brain)

Page 5: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M (1981)J. exp. Biol., 95, 111-127

K+ & Spreading Depression Instability theshold for K-induced K release

(Hodgkin, Grafstein, Tuckwell & Miura)Rapid K+ rise & recovery

in SD

Page 6: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M (1981)J. exp. Biol., 95, 111-127

SD (like the Migraine Aura) can be aborted by breathing O2+CO2

[Urethane anaesthetised rat]

Page 7: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

Current patterns around the SD K+ disturbance

G-M (1992) in Spreading Depression, ed. RJ Do Carmo. Exp. Brain Res. Series 23,62-74

Page 8: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M, van Bruggen, Williams & Ahier (1994)J. Cerebral Blood Flow & Metabolism 14,7-11

Functional MRI : Propagation of SD waves in rat brain

[Regions of increased gradient echo (oxygenation sensitive) intensity superimposed on a spin echo image). Frame interval 12.2 s, after 150mM KCl application in a craniotomy chamber. Halothane anaesthetised rat, ]

MRI : the movie !

Page 9: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M, Tepley, Barkley, Moran, Nagel-Leiby, Simkins & Welch (1991) Brain Research 540, 153-158.

Slowly changing magnetic Signals from SD in rabbit brain

[Urethane anaesthetised rabbit]

Page 10: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M (1986) Ann NY Acad Sci, 481, 287-302

K+ load (mol/s/L

)

q

Complex Buffer Capacity: combining buffer mechanisms with different dynamics

Page 11: Spatial Buffering of K+ in Relation to Spreading Depression Models Tony Gardner-Medwin Physiology (NPP), University College London

G-M (1986) Ann NY Acad Sci, 481, 287-302

Buffering through netK+ uptake into cells

Buffering through diffusion in EC spaceand Spatial Buffering

Buffering Capacities relevant to preventing propagation of Spreading Depression