Physiology for MRCEM Primary

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Basic cellular physiology

Membrane structure and membrane transport

Membrane structure

The bilayer structure embedded with transport proteins

The importance of G-protein coupled receptors in activation of cellular activity ( detailed knowledge of Gs, Gi, Gq types is NOT required).

Curriculum

Membrane lipids consist of a hydrophilic (water-loving) head, with two short hydrophobic (water-repelling) fatty acid tails. They are arranged in a bilayer with the heads facing outwards and the tails inwards. They diffuse freely within the layer (lateral diffusion).

Cell membrane strucure
Cell membrane structure – Image modified from Cell Membranes – Composition and Passive Transport | OER Commons Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License.

Lipid-soluble (hydrophobic / lipophilic) substances get incorporated into the membrane. If a molecule contains both hydrophobic and hydrophilic parts, they can be tethered part in and part out of the membrane.

Cell signaling

Transmembrane proteins (the proteins that span cross both layers of membrane) such as integrins and cadherins provide structural and signaling links.
Membrane-spanning proteins like ion channels and receptors allow signals to be transferred across the membrane.

Most of the receptors are from G-protein coupled receptor (GPCR) family with 7 membrane-spanning domains. When a ligand (e.g. neurotransmitter, hormone) attaches to the receptor, the receptor gets activated.
When a molecule (ligand) binds to its receptor, it leads to activation of enzymes to generate second messengers (like substrates for other enzymes or help activate protein kinases or trigger a rise in cytosolic Ca2+)

Protein kinases recognize target proteins by specific amino acid sequences (known as motifs).
Same motif can be seen in different proteins, so a protein kinase will be able to phosphorylate multiple targets and the result depends on cell type.
And a single motif can be recognized by more than one kinase.

Membrane transport

An understanding of the functioning of the Na-K ATPase transporter (sodium pump)

Appreciation that the sodium pump acts to move ions against concentration gradients

The principle of ion channels controlled by electrical or ligand gating

Curriculum

Lipid-soluble molecules (such as O2 and CO2) and small molecules (such as water and urea) can easily pass through the cell membranes.
But larger molecules such as glucose and charged molecules (ions) need transporters or ion channels to go from one side of the cell to the other side.
Proteins or larger molecules can enter the cells via endocytosis (engulfed by membrane segments). Upon entering the cell, the engulfed segments from intracellular vesicles.

Ligand gated Vs Voltage gated

When an ion channel gets activated when a substance like a neurotransmitter attaches to it is called as Ligand gated.

The ion channels / receptors at Post synaptic terminal of skeletal muscle (the neuromuscular junction NMJ) get activated due to Acetyl choline release at NMJ, so they are ligand gated.

Frequently tested

When an ion channel is activated due to electrical signal (like an action potential / membrane potential), it is called Voltage gated ion channel. Example – Voltage gated Sodium and potassium channels.

Sodium pump

The concentration of ions varies from intracellular compartment to the extracellular compartment.
The concentration of Sodium is higher in extracellular compartment and the Potassium content is higher inside the cell.
The concentration gradient will try to push Sodium in and Potassium out.
If this is not controlled, eventually, intra and extra cellular compartments will have equal quantities of ions.

This is where the Sodium pump – Na+-K+-ATPase comes into picture to preserve variable ion concentrations across the cell.

For each 3 Sodium ions pumped out, it’ll pump 2 Potassium ions into the cell. Both these movements are against the concentration gradient. So it’ll use energy via ATPase.

Any transport utilizing energy directly is known as ACTIVE transport.