Cellular Neurophysiology (NEUR0007) Notes - Transport & Glial Cells
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Course
Cellular Neurophysiology (NEUR0007)
Institution
University College London (UCL)
Explore Cellular Neurophysiology at UCL with a focus on Transport & Glial Cells. Uncover the dynamics of active transport in the nervous system, explore the role of gap junctions, and delve into the critical functions of glial cells in maintaining homeostasis within the extracellular space. Please ...
Active Transport in the Nervous System
Active Transport
Transport of substances across membranes – against their electro-chemical gradient
o Electro-chemical gradient = combination of electrical and concentration gradient
Power sources for active transport
o ATP hydrolysis
E.g.
Na+/K+ pump
Ca2+-ATPase
o Ion gradients
E.g.
Na+-glucose transporter
Na+/H+ exchanger
Na+/Ca2+ exchanger
Function
o Na+ pumps
Establishes transmembrane ion gradients and voltages
o Na /H+, Na+/HCO3-
+
pH regulation
o Na+-lactate, Na+-glucose
Solute accumulation
o Na -glutamate, Na+-GABA
+
Termination of synaptic transmission
o Na+/Ca2+, Ca2+-ATPase
Second messenger regulation
Power
o To transport a mole of substance against a concentration gradient – from C 1 to C2 = requires energy
RTln(C2/C1)
I.e. – 5.9kJ/mol per 10-fold concentration change
o Transport of negatively charged molecule into cell (V m = -ve) more energy is needed to overcome
the electrical force
FVm = 5.8kJ/mole – for Vm = -60mV
o Source of power
ATP splitting
ATP ADP + Pi – gives ou 50kJ/mol
Transport of other ions
Transport of one Na+ into cell – gives 5.9kJ from the concentration gradient + 5.9kK
from the electrical gradient = total 11/7kJ/mol
Na+/K+-ATPase
o Structure
2 α subunits 112 kD
ATP binds on inner face of α subunits
2 β subunits 40 kD
β not needed for pumping
o Observations
ATP not hydrolysed unless Na+ and K+ are transporter
ATPase found wherever Na+ and K+ are pumped
ATPase and pump are both in membrane + both are inhibited by
ouabain – stimulated by Na+ and K+
Conclusion – ATPase is the pump
o Binding
, Active Transport in the Nervous System
ATP binding to α subunits triggers pumping out of 3Na+ + entry of 3K+
Na+ binds inside triggers conformational change allowing ATP to
phosphorylate the pump on an aspartate residue gives a large negative charge to
the protein leading to conformational change allows Na+ to leave the cell
K+ binds outside triggers conformational change K+ enters the cell allows
dephosphorylation of the pump
o Energy needed
Move 2K+
Requires little energy – as Vm is close to EK
o Resting potential is close to Nernst potential for K + (voltage at which
electrical gradient which pulls K+ into the cell = concentration gradient that
pulls K+ out of the cell)
+
Move 3Na
3 x 11.7kJ = 35kJ
o Energy from ATP
50kJ/mole
Ca2+-ATPase
o Variants
PMCA – plasma membrane Ca2+-ATPase
SERCA – sarcoplasmic and endoplasmic reticulum Ca 2+-ATPase
Number of ions transported may differ
A major Ca2+ extrusion mechanism – uses 1 ATP to extrude 1
ca2+ from cytoplasm outside cell or sarcoplasmic reticulum – in
exchange for 2 H+
o Transporters have a high affinity for Ca2+ - but work slowly
Sequence homologous to a subunit of Na + pump
An aspartate is phosphorylated during carrier cycle – P-type ATPase
ATP is only hydrolysed when Ca2+ is pumped
o What Ca2+ concentration gradient can the pump transport Ca 2+ against
Energy from ATP = 50kJ/mol
No energy needed for charge transfer
As Ca2+ cancels 2 H=
Energy to move 2 H+ into cell
Up to 2-fold concentration gradient
2xRTln(2) = 3.6kJ
50-3.6 = 46.4kJ
Energy to move Ca2+ into SR or out of cell is 5.9kJ/10-fold concentration gradient
So can accumulate against a gradient of 10 N – where N = 46.4/5.9 = 7.9
Thus – for 10mM Ca2+ in SR – can lower cytoplasm Ca2+ concentration to 10-2/107.9 = 10-9.9M
Reversal of ATPases
o ATP hydrolysis is tightly coupled to ion movements
With appropriate ion gradients – Na/K and Ca-ATPases – can run
backwards = getting energy from ion gradients to make ATP
E.g.
o K+ inside cell but not outside
o Na+ outside but not inside
o Internal ADP is converted into ATP
+
o H -ATPase
In mitochondria
Runs backwards – making ATP at the expense of the proton gradient
Proton gradient = generated by proton pumping fuelled by metabolim
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