1 the membrane potential results from: (1) action of na-k pump (2) permeability of pm (leakage...
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The Membrane Potential Results from:
(1) action of Na-K pump
(2) permeability of PM (leakage channels)
(3) presence of impermeant molecules (fixed anions)
yields an observed “charge” at the PM (outside is slightly more positive,
inside is slightly more negative)
-+
membrane potential
leakage channels
Na Kfixed anions
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difference in charge, or potential difference, is the
membrane potential; denoted in volts
primarily determined by K conc gradient
For a cell:
Na-K pump
leakage channels
fixed anions
The Membrane Potentialof a Cell
*is only observed at the PM*
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Equilibrium Potentials
• many inorganic ions maintained at specific conc’s within IC & EC– contributes to membrane potential,
impact of each ion depends on it’s:• conc gradient• membrane permeability
– K• major role in membrane potential
– PM more permeable to this ion
• consider membrane only permeable to K, what would be the membrane potential?– K equilibrium potential, EK
• -90mV (with an internal concen of 150 and external of 5) As the membrane potential is -90, K will not move.
– Na equilibrium potential, ENa• 66 mV (when concentration is 145
outside and 12 mM inside) Na will not move
equilibrium
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equilibrium potentials are useful for they explain what happens when the PM becomes more permeable to a particular ion
example – an excitable cell
at rest
-70mV
permeable to Na, brief pd; membrane potential
moves toward ENa
YET, the membrane potential at rest is close
but not the same as the EK
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Nernst Equation
• diffusion gradients of an ion depend on conc differences
• equilibrium potential depends on ratio of ion conc on both sides of PM
• Nernst equation – permits calculation of theoretical
equilibrium potential for specific ion• conc’s known
• differ between ion species– magnitude & direction– cation
• value negative– Xi > Xo (internal conc greater
than outside) – K is (-90) high inside cell– Na is (66) high outside cell
• yet, what happens when more than one ion channel is open?– GHK equation (Vm)
EX = _______ log ______61
z
[Xo]
[Xi]
61 mM= ____ log __5___ = -90 +1 150 mM
= _61_log _____ = +66 mV +1
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– Goldman-Hodgkin-Katz equation (Vm)
Vm = 61 logPK [Ko] + PNa[Nao] + PCl[Cli]
PK [Ki] + PNa[Nai] + PCl[Clo]
(1)(5) + (0.04)(145) + (0.45)(9)= 61 log = -68 mV (1)(150) + (0.04)(12) + (0.45)(125)
Reversed due to Cl is an anion mvt has oppositite effect on membrane
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Resting Membrane Potential (RMP)
• membrane potential of a cell at “rest”, or a cell in an inactivated state
• depends on:– ratio of conc’s (Xo/Xi) of each ion on both sides of PM– specific permeability of membrane to each ion
• most impt “players”– K+, Na+, Ca2+ & Cl-
• individual contribution dependent on conc differences across PM (can change depending on cell type, tissue or organ) & permeabilities
– any change in an ions EC conc will change the RMP but only to the extent the membrane is permeable (you can mess with Na conc gradient, but have more impact if you mess with K)
– change in the cell membranes permeability for any given ion will change its RMP
» excitable cells• cellular range
– -65 mV to -85 mV
Question• Would lowering a neuron’s IC [K] by 1 mM
have the same effect on RMP as raising the EC [K] by 1 mM?
• Confirm with Nernst equation
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-No; Changing the EC [K] has a greater effect on Ek and thus the RMP. This is because of the ratio of external to internal K is changed more when EC levels go from 5 to 6 mM (20% increase) than IC level lowered from 150 to 149 mM (0.7% increase)
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Role of Na-K pumps
RMP is less than the EK suggest that K leaks out & cell not at equilibrium with respect to K conc, or Na conc either
runs continuously
maintains ion conc’s
counters leakage
electrogenic effect
unequal transport of + charge (3Na to 2K) by Na-K pump, makes inside “less” positive, or negative
MINIMAL on RMP
leakage channels always open
ion leakage + EE, results in
membrane potential
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Influences on RMP
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Cell Signaling • refers to how cells communicate with each other– intercellular
communication• many release regulatory
molecules into EC environment
– general categories» paracrine
» synaptic
» endocrine
local mechanism
functional connection
long distance
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A = autocrine
GAP JUNCTIONS provide direct communication between cells by
fusing PMs and permitting diffusion from one cell’s cytoplasm to the next
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Regulatory Molecules
target cell
target cell must display a R protein for signaling/regulatory molecule
LOCATION
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Signal Transduction Pathways
mech for water soluble msgers
2nd messenger systems
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Signal Transduction Pathways
transcription factor
mech for lipid-soluble msger
Cessation of Activity in Signal Transduction
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• impt b/c chronic overstimulation can be detrimental to cell
detrimental to the cell
• key event is stopping R activation– (1) decrease conc of 1st msger– (2) R becomes chemically altered, lowers affinity for 1st msger– (3) R becomes phosphorylated, prevents G-protein binding– (4) R-ligand complex endocytosed, removed R from PM