Physiology

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1. Cell physiology

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Characteristics of cell membranes

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Phospholipid component of cell membranes

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• phospholipids for a lipid bilayer

Protein component of cell membranes

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• integral membrane proteins are embedded in the cell membrane due to hydrophobic interactions
  • they are covalently bound to cell membrane copmponents.
  • some integral membrane proteins may be transmembrane proteins: proteins that span the lipid bilayer one or more times, and therefore are in contact with both ECF and ICF.
• peripheral membrane proteins
  • not embedded and not covalently bound to cell membrane components
  • loosely attached to cell membrane through electrostatic interactions (e.g. with integral proteins)
  • e.g. ankyrin in red blood cells links cytoskeleton to the integral membrane transport protein $\ce{Cl-}$-$\ce{HCO3-}$ exchanger ("band 3 protein")

Transport across cell membranes

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• all forms of carrier-mediated transport (i.e. all forms of transport other than simple diffusion) share the following three features: saturation, stereospecificity, and competition.
  • saturation
    • based on the fact that carrier proteins have a limited number of binding sites for the solute
    • saturation is achieved at the transport maximum, denoted $T_m$.
  • stereospecificity
    • binding sites for solute are stereospecific
  • competition
    • binding sites are not perfect; they can recognize, bind, and sometimes transport cheimcally related solutes.

Simple diffusion

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Diffusion of nonelectrolytes

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• flux (=flow). denoted $J$, flux is the net diffusion of solute.
  • $J_{A\to B}$ [$\pu{mmol/s}$] $= PA(C_A - C_B)$
    • size of the concentration gradient ($C_A - C_B$)
    • partition coefficient ($K$)
    • diffusion coefficient ($D$)
    • thickness of the membrane ($\Delta x$)
    • surface area available for diffusion ($A$)
• concentration gradient
  • higher concentration gradient = more diffusion
• partition coefficient
  • $K = \dfrac{\text{concentration in olive oil}}{\text{concentration in water}}$
  • a measure of a solute's ability to pass through the cell membrane
  • higher partition coefficient = more diffusion
• diffusion coefficient
  • defined by the Stokes-Einstein equation
  • $D = \dfrac{KT}{6\pi r\eta}$
    • $K$ = Boltzmann constant
    • $T$ = Absolute temperature (in Kelvins)
    • $r$ = Molecular radius
    • $\eta$ = Viscosity of the medium
  • higher diffusion coefficient = more diffusion
• thickness of the membrane
  • thicker membrane = less diffusion
• surface area
  • greater surface area = more diffusion
• permeability ($P$)
  • $P = \dfrac{KD}{\Delta x}$ [$\pu{cm/s}$]
  • combines concentration and diffusion gradient with membrane thickness

Diffusion of electrolytes

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• two additional factors
  • membrane potential
  • diffusion potential. the membrane potential generated as a result of the electrolyte itself diffusing

Facilitated diffusion

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• uses a membrane carrier and thus exhibits all characteristics of carrier-mediated transport:
  • saturation
  • stereospecificity
  • competition
• at low concentrations, facilitated diffusion is faster than simple diffusion; but at high concentrations, facilitated diffusion saturates and can become slower than simple diffusion
• example: D-glucose and GLUT4 transporter.
  • D-glucose is transported into skeletal muscle and adipose tissue by the GLUT4 transporter
  • D-galactose, 3-O-methyl glucose, phlorizin competitively inhibit GLUT4

Primary active transport

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• active transport. movement of a solute up the electrochemical gradients requires work
• primary active transport. direct coupling of ATP phosphate transfer to the transport of solute

$\ce{Na+}$-$\ce{K+}$ ATPase

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• transport process is electrogenic; creates a charge separation and potential difference
• consists of $\alpha$ and $\beta$ subunit
  • $\alpha$ subunit contains ATPase activity and binding sites for $\ce{Na+}$ and $\ce{K+}$
• ATPase cycles between two states $\mathbf{\mathrm{E_1}}$ (facing ICF, binding $\ce{Na+}$) and $\mathbf{\mathrm{E_2}}$ (facing ECF, binding $\ce{K+}$)
• cardiac glucosides (e.g. ouabain, digitalis). inhibit $\ce{Na+}/\ce{K+}$ ATPase
  • binds to $\mathrm{E_2}\text{:P}$ form and prevents return to $\mathrm{E_1}$

$\ce{Ca^2+}$ ATPase

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• plasma membrane calcium ion ATPase (PMCA). 1 calcium ion pumped per ATP
• SERCA. sarcoplasmic reticulum (SR) (muscle cells) and endoplasmic reticulum (ER) (other cells) variants of PMCA that pump two $\ce{Ca^2+}$ for each ATP
• also has $\mathrm{E_1}$ and $\mathrm{E_2}$ states
  • $\mathrm{E_1}$ always faces the cytosol

$\ce{H+}$-$\ce{K+}$ ATPase (HK-ATPase)

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• found in parietal cells of gastric mucosa and $\alpha$-intercalacted cells of the renal collecting duct
  • pumps $\ce{H+}$ into the lumen of the stomach
  • omeprazole inhibits HK-ATPase

2. Autonomic nervous system

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