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lidocaine
exists in ionized or unionized forms
given pKa of 7.9, about 25% of lidocaine is present in non-ionized form at physiological pH of 7.4
cell membrane
bilayer sheet that functions to separate extracellular and intracellular environments and create internal compartments that allow specific tasks to be achieved separately
selectively permeable and contains receptors that allow for communication
does not live in isolation → interacts with extracellular matrices, neighboring cells, cytoskeletal structures
interactions can change gene expression and influence things on inside
can have different properties depending on location → apical domain vs basolateral domain
polar heads bind electron-dense metals to allow for staining
communication vis receptors and signaling pathways
maintains homeostasis through ion gradients and compartmentalization
lipid composition in cell membrane
phospholipid: can be neutral or anionic (negatively charged)
nomenclature of glycerophospholipid → phosphatidyl [head group]
amphiphatic, asymmetrically distributed, flipping limited to use of enzyme
can have different types of phospholipids intermingled among each other
cis double bond prevents close packing of fatty acids
sphingolipids: important for signaling and structural stability
cholesterol: amphiphatic sterol with polar head group and nonpolar hydrocarbon body
membrane constituent that participates in membrane fluidity and integrity
low temperature → cholesterol maintains fluidity; high temperature → cholesterol decreases fluidity
protein composition in cell membrane
proteins function for transport, signal reception, adhesion, enzymatic activity, and cytoskeletal linkage
integral: amphiphatic proteins that are embedded in membrane
removed using detergents
asymmetrically distributed in membrane
peripheral: interacts with some part of membrane
removed by removing its ionic interactions
lipid-anchored: bound and anchored to one leaflet
fatty acyl group → anchors protein to inner leaflet
GPI-linkage → anchors protein to outer leaflet
glycoprotein: integral proteins that are asymmetrically distributed
N-linked sugars face extracellular environment
intrachain disulfide bonds face extracellular environment
sulfhydryl groups face cytosol
membrane asymmetry patterns
inner leaflet → phosphatidylserine and phosphatidylinositol give negative charge and responsible for signaling
PS flips to outer leaflet during apoptosis for signaling to immune cells
outer leaflet → glycolipids and sugars for recognition and protection
glycocalyx
carbohydrate-rich layer on cell exterior
made from sugars attached to proteins or lipids
function for cell-cell recognition, protection from mechanical or chemical damage, prevents unwanted protein adhesion, and selective absorption (in GI tract)
epithelial polarity
apical surface: faces lumen, specialized for absorption and secretion
basolateral surface: faces neighboring cells and extracellular matrix, contains pumps and transporters
tight junctions: act as “fences” to keep domains separate and maintain function
loss of polarity causes loss of directional transport and tissue dysfunction