Chapter 4 – The Cell Membrane




Abstract




The cell membrane is the lipid bilayer structure that separates the intracellular contents from the extracellular environment. It controls the passage of substances into and out of the cell. This allows the cell to regulate, amongst other parameters, intracellular ion and solute concentrations, water balance and pH. The integrity of the cell membrane is of crucial importance to cell function and survival.





Chapter 4 The Cell Membrane



The cell membrane is the lipid bilayer structure that separates the intracellular contents from the extracellular environment. It controls the passage of substances into and out of the cell. This allows the cell to regulate, amongst other parameters, intracellular ion and solute concentrations, water balance and pH. The integrity of the cell membrane is of crucial importance to cell function and survival.



What is the structure of the cell membrane?


The cell membrane is composed of two layers of phospholipid, sandwiched together to form a phospholipid bilayer (Figure 4.1). Important features of this structure are:




  • The phospholipid is composed of a polar hydrophilic phosphate head to which water is attracted and a non-polar hydrophobic fatty acid tail from which water is repelled.



  • The phospholipid bilayer is arranged so that the polar groups face outwards and the non-polar groups are interiorised within the bilayer structure.



  • The outer surface of the phospholipid bilayer is in contact with the extracellular fluid (ECF) and the inner surface of the bilayer is in contact with the intracellular fluid (ICF).



  • The non-polar groups form a hydrophobic core, preventing free passage of water across the cell membrane. This is extremely important as it enables different concentrations of solutes to exist inside and outside the cell.



  • The phospholipid bilayer is a two-dimensional liquid rather than a solid structure; the individual phospholipids are free to move around within their own half of the bilayer. The fluidity of the cell membrane allows cells to change their shape; for example, red blood cells may flex to squeeze through the small capillaries of the pulmonary circulation.





Figure 4.1 The phospholipid bilayer.



Which other structures are found within the cell membrane?


A number of important structures are found in and around the cell membrane:




  • Transmembrane proteins. As suggested by the name, these proteins span the membrane phospholipid bilayer. Importantly, the fluidity of the cell membrane allows these transmembrane proteins to float around, rather like icebergs on a sea of lipid.



  • Peripheral proteins. These proteins are mounted on the surface of the cell membrane, commonly the inner surface, but do not span the cell membrane. Cell adhesion molecules, which anchor cells together, are examples of outer membrane peripheral proteins. Inner membrane peripheral proteins are often bound to the cytoskeleton by proteins such as ankyrin, maintaining the shape of the cell.



  • Glycoproteins and glycolipids. The outer surface of the cell membrane is littered with short carbohydrate chains, attached to either protein (when they are referred to as glycoproteins) or lipid (when they are referred to as glycolipids). The carbohydrates act as labels, allowing the cell to be identified by other cells, including the cells of the immune system.



  • Cholesterol. This helps strengthen the phospholipid bilayer and further decreases its permeability to water.



What are the functions of transmembrane proteins?


The hydrophobic core of the phospholipid bilayer prevents simple diffusion of hydrophilic substances. Instead, transmembrane proteins allow controlled transfer of large or charged solutes and water across the cell membrane.


The cell can therefore regulate intracellular solute concentrations by controlling the number, permeability and transport activity of its transmembrane proteins. There are many different types of transmembrane protein – the important classes are:




  • Ion channels, water-filled pores in the cell membrane that allow specific ions to pass through the cell membrane along their concentration gradients.



  • Carriers, which transport specific substances through the cell membrane via facilitated diffusion.



  • Pumps (ATPases) use energy (from ATP hydrolysis) to transport ions across the cell membrane against their concentration gradients.



  • Receptors, to which extracellular ligands bind, initiating an intracellular reaction either via a second messenger system (metabotropic) or an ion channel (ionotropic).



  • Enzymes, which may catalyse intracellular or extracellular reactions.



By what means are substances transported across the cell membrane?


The behaviour of substances crossing the cell membrane is broadly divided into two categories:




  • Lipophilic substances (e.g. O2, CO2 and steroid hormones) are not impeded by the hydrophobic core of the phospholipid bilayer and are able to cross the cell membrane by simple diffusion (Figure 4.2). Small lipophilic substances diffuse through the cell membrane in accordance with their concentration or partial pressure gradients: molecules diffuse from areas of high concentration (or partial pressure) to areas of low concentration (or partial pressure) (see Chapter 10).



  • Hydrophilic substances (e.g. electrolytes and glucose) are prevented from passing through the hydrophobic core of the phospholipid bilayer. Instead, they traverse the cell membrane by passing through channels or by combining with carriers.


Hydrophilic substances can be transported across the cell membrane by passive or active means (Figure 4.2):




  • Passive transport. Some transmembrane proteins act as water-filled channels through which hydrophilic molecules can diffuse along their concentration gradients. These protein channels are highly specific for a particular substance. There are two types of passive transport – ion channels and facilitated diffusion:




    1. Ion channels are pores in the cell membrane that are highly specific to a particular ion. For example, the pore component of a voltage-gated sodium channel is the right size and charge to allow Na+ to pass through 100 times more frequently than K+ ions.1 Ion channels may be classified as:




      1. Leak channels, which are always open, allowing continuous movement of the specific ion along its concentration gradient.



      2. Voltage-gated channels, which open by changing shape in response to an electrical stimulus, typically a depolarisation of the cell membrane (see Chapter 52).2 When the ion channel is open, the specific ion diffuses through the cell membrane along its concentration gradient, but when the channel is closed or inactivated the membrane becomes impermeable.



      3. Ligand-gated channels, where the binding of a small molecule (ligand) causes the ion channel to open or close. For example, acetylcholine (ACh) binds to the nicotinic ACh receptor (a ligand-gated cation channel) of the neuromuscular junction, thereby opening its integral cation channel (see Chapter 53).



      4. Mechanically gated channels, which have pores that respond to mechanical stimuli, such as stretch. For example, mechanically gated Ca2+ channels open following distension of arteriolar smooth muscle – this is the basis of the myogenic response (see Chapters 34 and 56).




    2. Facilitated diffusion. A carrier protein binds a specific substrate before undergoing a number of conformation changes to move the substrate from one side of the cell membrane to the other. Once the substrate has passed through the cell membrane, it is released from the carrier protein. The substance passes down its concentration gradient, facilitated by the carrier protein (Figure 4.3). Facilitated diffusion is much faster than simple diffusion, but is limited by the amount of carrier protein in the cell membrane. The most important example of facilitated diffusion is glucose transport into the cell through the glucose transporter (GLUT). An example of passive counter-transport is the Cl‾/bicarbonate (HCO3‾)-antiporter in the renal tubule, where Cl‾ and HCO3‾ are simultaneously transported in opposite directions down their respective concentration gradients.




  • Active transport. Energy from ATP hydrolysis is used to move substances across the cell membrane. Active transport is further subclassified as:




    1. Primary active transport. Here, ATP is hydrolysed by the carrier protein itself as it moves ions from one side of the cell membrane to the other. An example of primary active transport is the plasma membrane Ca2+-ATPase, which pumps Ca2+ out of the cell, keeping the intracellular Ca2+ concentration very low. An important example of a more complicated system of primary active transport is the Na+/K+-ATPase pump, which uses one molecule of ATP to transport three Na+ ions from the ICF to the ECF, whilst simultaneously transporting two K+ ions from the ECF to the ICF. Unlike passive transport, whose direction of diffusion depends on the relative concentrations of the substance on either side of the cell membrane, active transport is usually unidirectional. The Na+/K+-ATPase can only move Na+ intracellularly and can only move K+ extracellularly.



    2. Secondary active transport, a combination of primary active transport and facilitated diffusion. Substances are transported alongside Na+, driven by the low intracellular concentration of Na+, which in turn is generated by the Na+/K+-ATPase pump. So whilst the transporter is not directly involved in hydrolysing ATP, it relies on primary active transport, which consumes ATP. Secondary active transport may be:




      1. Co-transport (or ‘symport’), where both ions move in the same direction, such as the absorption of glucose with Na+ in the renal tubules through the sodium–glucose-linked transporter (SGLT-2).3



      2. Counter-transport (or ‘antiport’), where each ion is transported in opposite directions, such as the Na+/K+-antiporter in the principal cells of the renal collecting ducts.




Sep 27, 2020 | Posted by in ANESTHESIA | Comments Off on Chapter 4 – The Cell Membrane
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