Ionic Basis of Membrane Potential
Transcription
Ionic Basis of Membrane Potential
Ionic Basis of Membrane Potential Dr Sergey Kasparov School of Medical Sciences, Room E9 Teaching Teaching home home page: page: http://www.bristol.ac.uk/phys-pharm/personal/virallab/teaching/downloads.php http://www.bristol.ac.uk/phys-pharm/personal/virallab/teaching/downloads.php 1.Phospholipid bi-layer is the key component of all cellular membranes. Water Water (aqueous) (aqueous) phase: phase: charged, charged, polar polar molecules molecules and and ions ions can can dissolve dissolve and and move. move. Water Water (aqueous) (aqueous) phase: phase: charged, charged, polar polar molecules molecules and and ions ions can can dissolve dissolve and and move. move. Lipid Lipid (hydrophobic) (hydrophobic) phase: phase: charged, charged, polar polar molecules molecules cannot cannot dissolve dissolve and and move. move. 2.Bioelectricity is generated by the ions moving across cellular membranes. Concentration Concentration of of selected selected solutes solutes in in intracellular intracellular fluid fluid and and extracellular extracellular fluid fluid in in millimols millimols mM mM160 160 140 140 120 120 100 100 Inside Inside the the cell cell 80 80 In In extracellular extracellular fluid fluid 60 60 40 40 + CCa a 22+ + MMg g 22+ NNa a ++ KK ++ 00 IInno CCl orr lH H g gaa C C nniic OO3 c P 3 -Phh oo AAm sspph mi h inno aatte oa e acc iidds s GGl luuc coo ssee AAT TPP PPrr oott eeiin n 20 20 Remember these numbers (they may vary to some extent in different cells) IN OUT K++ 140 4 Na++ 15 145 0.001 1.8 4 115 2+ Ca2+ Cl-- CONCENTRATIONS CONCENTRATIONS ARE ARE IN IN MILLIMOLS MILLIMOLS If the membrane was freely permeable to these ions… their concentration would be identical on both sides. 3. 3. Ions Ions cannot cannot pass pass through through the the membranes membranes –– they they are are too too hyrdophylic hyrdophylic for for that. that. Therefore Therefore they they use use channels channels –– special special proteins proteins embedded embedded into into the the plasma plasma membrane. membrane. Forces which determine the direction of transport across the membrane Passive vs active transport Passive - along the concentration gradient and using the energy of this gradient Active – uses energy supplied by the cell to special proteins called PUMPS - against the concentration gradient These guys guys are are It is the pumps which are responsible for the generation of These called called pumps! pumps! ionic gradients across the membranes of neurones Chemical vs Electrical Driving Force Chemical driving force Chemical vs Electrical Driving Force + + + + + + + + + + + + + + + + + + + + + + + + + + + _ _ _ _ _ _ _+ _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + + Electrical driving force + + _ _ _ _ _ _ _+ _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + + + + + + + + + + + + + + + + + Chemical and Electrical Driving Forces may combine to create the Electrochemical Driving Force +_ _+ + _ +_ +_ + _ _ + + _ + _ + + + + + + + _+ _ + + _ 4mM + Chemical driving force + + _ Electrical driving force + + + + + _ + What will happen if the potential of this mV _ + _ -70 _ _ membrane decreases to -10 mV? + + Chemical driving force + + 140 mM + K++ Electrical driving force Conclusion: movement of charged particles such as ions, across the membrane depends on electro-chemical driving force (the sum of the force generated by chemical gradient and the force generated by electric field). Chemical driving force Electrical driving force _ _ _ _ _+ _ _ _ _ _ + + + + + + + + + + + + Net flux + + V + + + + + + + Chemical driving force Electrical driving force _ _ _ _ _ _ _ _ + _ _ _ _ _ _ _ _ _ _ _ _ _ _ + + + + + + + + + + + + Net flux + + ++ + + + + ++ ++ + + + + + + + V Chemical driving force Electrical driving force _ _ _ _ _ _ _+ _ _ _ _ _ _ _ _ + + + + + + + + + + Net flux + + + V + + + + + + + + + + + + The Reversal Potential: Potential of the membrane at which the electrical driving force is exactly equal the chemical driving force and therefore THE NET FLUX of this particular ion is NIL. Reversal potential can be calculated using Nernst equation: 61.5mV Log (C /C Eion = out Z in) 61.5 is a calculated constant derived from Universal gas constant, the temperature (37oC) and Faraday electrical constant Z – is a valence of an ion Using this equation: ENa Na = 61.5/1 * log (145/15) ≈ 60.5 mV EKK = 61.5/1 * log (4/140) ≈ -95 mV This means that in a hypothetical neurone sodium flux through the open channels will tend to bring membrane potential toward +60.5 mV, while potassium flux will bring it toward -89 mV. But But this this could could only only happen happen if if these these ions ions were were allowed allowed to to freely freely flow flow through through the the membrane… membrane… and and they they are are not! not! Because the membrane is essentially impermeable to ions, they have to use ion channels to pass between intra- and extracellular space. AA leak leak channel channel AA gated gated channel channel 1. When neurone is at “rest” its membrane potential is negative, this is called “resting membrane potential”. 2. At rest the main ion flux is K++, but also there are small Na+ and Cl-fluxes. Since the potential at “rest” does not change, it means that the sum of these currents is zero. 3. Permeability of the membrane to an ion (NOT actually the membrane but the channels passing that particular ion) may vary, because the channels may open and close. The equation which takes into account impacts of all these 3 ions and predicts the resting membrane potential is called “Goldman-HodgkinKatz” or “Goldman” or “Constant Field” equation. Vm = 61.5 mV x log ( P ) ] PK [Kout] +PNa[Naout] + PCl[Clin] K [Kin] +PNa[Nain] + PCl[Clout