Lecture 6 Flashcards

Regulation of Ca2+ and Na+

1
Q

Extracellular concentration of Na+

A

145mM

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2
Q

Intracellular concentration of Na+

A

15mM

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3
Q

Thick Ascending Limb of Henle’s Loop

A

Function - absorbs Na+ and Cl- in preference to water
Apical NKCC2 co-transporter relies on the inward gradient couple inward movement of Na+, 2k+ and Cl-
Transepithelial osmotic gradient responsible for counter current multiplication

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4
Q

IC Na+ high effects on the thick ascending limb

A

NaCl reabsorption reabsorption would be inhibited and trans epithelial osmotic gradient dissipated

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5
Q

Electrically excitable cell

A

ENa = +60mV
EK = -70mV
Vm = -70mV
There is an inward chemical and electrical gradient for Na_

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6
Q

IC Na+ high effects on Electrically excitable cells

A

Decrease in the inward chemical gradient
ENa would so driving force for Na+ influx is decreased
Would take longer for the action potential to develop, peak of the action potential would be lower and conduction of the action potential would be slow

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7
Q

Na+/K+ ATPase moel of action

A

Na+ binds to cleft in the pump
Hydrolysis of 1 ATP
Phosphorylation of the pumo
Conformational change of the binding site so the cleft is exposed to the extracellular side
K+ binds to the binding domain
Dephosphorylation of pumo
Conformational change - binding domain now exposed to the intracellular side and K+ released

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8
Q

What inhibits Na+/K+ ATPase?

A

Cardiac glycosides

e.g. Ouabain and digoxin

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9
Q

Na+/K+ ATPase rate

A

The saturable function of intracellular Na+ and extracellular K+
Will reach a plateau
Also satiable function of ATP
So will depend on the metabolic state of the cell

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10
Q

Na+/k+ ATPase roles in Vm determination

A

Sets up high IC K+ and low K+ EC causing a leak current, so the driving force for K+ to leave so the inside of the cell more negative
Electrogenic - loss of 1 positive charge

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11
Q

Extracellular concentration of Ca2+

A

1mM

1000000nM

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12
Q

Intracellular concentration of Ca2+

A

100nM

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13
Q

Ca2+ concentration importance

A

Important second messenger
1000 fold difference IC:EC
ECa2+ = +120mV
Gradient is favourable for Ca2+ gradient

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14
Q

Pancreatic Acinar Cell CK-8/Gastrin

A

Increases turnover of phosphatidylinositol
Releases cellular Ca2+ which increases cyclic AMP
Increases enzyme secretion

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15
Q

Pancreatic Acinar Cell Secretin, VIP

A

Increases cellular cyclic AMO

Increases enzyme secretion

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16
Q

Na+/Ca2+ exchanger

A

Ca2+ out and Na+ in
Relies on inward Na+ gradient
Can work in either direction
e.g. Reverses during systolic the cardiac myocytes

17
Q

Na+/Ca2+ exchanger Keeping low IC Ca2+ level

A

Electrogenic = 3Na:1Ca
Effect of Na+ gradient is magnified
Effect of ten fold gradient is cubed

18
Q

Na+/Ca2+ exchanger family

A

SLC8 family - superfamily CaCA
Three isoforms
Splice variants

19
Q

Na+/Ca2+ exchanger model

A
3 EC Na+ bind
Conformational change and released to IC
1Ca IC bind
Conformational change
Ca released to EC
20
Q

PMCA

A

Plasma membrane calcium pumps

Act to pump Ca2+ across the PM out of cell

21
Q

SERCA

A

Ca2+ pumps found on the sarcoplasmic or ER membranes

Act to pump Ca2+ out of the cytoplasm into the organelles which act as calcium stores

22
Q

SPCA

A

Golgi apparatus calcium pumos

Also transports Mn2+

23
Q

Ca2+ ATPases

A

Members of the P-type ATPase family - includes Na+/K+ pump

Can also transport proteins

24
Q

IP3 receptors

A

Store pathway
Channel activated following IP3 binding
Receptor expressed in most cell types

25
Q

Ryanodine receptors

A
Store pathway
Low conc. of ryanodine activate the channels
higher conc. inhibits
Also stimulated by caffeine
natural activator is cADP ribose
Tend to be found one excitable cells
26
Q

Store-operated Ca2+ channels

A

Signalling between the empty store and membrane store-operated Ca2+ channel
Physical interaction between the store and the membrane