Transport Mechanisms and Ion Channels - Self Assessment

1) Compare and contrast ion channel and transporter function.

• Ion Channels: Ion channels are proteins that form pores in the membrane, allowing ions to move passively down their electrochemical gradients. They are fast and selective for specific ions (e.g., Na⁺, K⁺). Channels can be gated by stimuli like voltage, ligands, or mechanical forces. They do not require energy (passive transport).

• Transporters (Carriers): Transporters bind specific molecules or ions and undergo conformational changes to shuttle them across the membrane. Transporters can facilitate both passive transport (facilitated diffusion) or active transport (against the gradient, requiring energy, often from ATP hydrolysis). They are slower than ion channels and often move larger molecules, like glucose or amino acids.

2) Plot the influx rate for glucose as a function of extracellular glucose concentration into a cell that expresses the facilitated diffusion glucose transporter.

The relationship between glucose concentration and influx rate in facilitated diffusion follows a hyperbolic curve, similar to Michaelis-Menten kinetics. Initially, as extracellular glucose concentration increases, the influx rate increases rapidly. However, at high glucose concentrations, the transporter becomes saturated, and the rate of influx reaches a maximum ($V_{\text{max}}$$V_{\text{max}}$).

Where:

• $V_{\text{max}}$$V_{\text{max}}$ is the maximum rate of glucose influx.

• $K_m$$K_m$ is the glucose concentration at half-maximal influx.

3) Why is ATP hydrolysis necessary for activity of the Na⁺/K⁺ ATPase?

ATP hydrolysis provides the energy required for the Na⁺/K⁺ ATPase to pump 3 Na⁺ ions out of the cell and 2 K⁺ ions into the cell against their concentration gradients. This active transport maintains the electrochemical gradient necessary for processes such as action potential propagation and secondary active transport.

4) What purpose does Na⁺ serve in the Na⁺/sugar cotransporter? Why aren’t the transporters K⁺/sugar cotransporters instead?

Na⁺ serves as a driving force in the Na⁺/sugar cotransporter by moving down its electrochemical gradient, which provides the energy to transport glucose into the cell against its concentration gradient. K⁺ is not used because its concentration gradient and electrochemical potential are less favorable for driving this process compared to Na⁺.

5) Describe the basic structure of an ion channel.

Ion channels typically consist of several subunits that form a pore through the membrane. The pore is lined by hydrophilic amino acid residues, allowing specific ions to pass through. Ion channels have gate mechanisms that can be opened or closed in response to various signals (voltage, ligands, etc.).

6) Describe how each of the four classes of ion channels works.

1. Voltage-gated ion channels: Open in response to changes in membrane potential.

2. Ligand-gated ion channels: Open when a specific ligand (such as a neurotransmitter) binds to the channel.

3. Mechanically-gated ion channels: Open in response to physical deformation of the membrane.

4. Leak channels: Are usually open and allow passive flow of ions to help maintain resting membrane potential.

7) Describe the fundamental structure of the functional voltage-gated and ligand-gated ion channel units.

• Voltage-gated channels: Typically composed of four subunits, each with six transmembrane segments. One of the transmembrane segments (S4) serves as the voltage sensor.

• Ligand-gated channels: Consist of multiple subunits (usually five) that come together to form a pore. The ligand-binding domain is located extracellularly, which controls the opening of the pore.

8) How is water selected over ions through an aquaporin?

Aquaporins are selective for water molecules due to their narrow pore size and the presence of specific amino acid residues that form hydrogen bonds with water molecules. The structure excludes ions like Na⁺ or K⁺ because they are too large or cannot form the necessary interactions to pass through the channel.

9) Describe the K⁺ channel selectivity filter.

The selectivity filter of the K⁺ channel consists of a narrow region lined with carbonyl oxygen atoms that mimic the hydration shell of K⁺ ions. This allows K⁺ to pass through while excluding smaller ions, like Na⁺, which cannot interact properly with the filter due to their smaller size.

10) Describe the pathophysiology of cholera, and how the inexpensive treatment with a high sugar, Na⁺ solution prevents death by dehydration.

Cholera causes severe diarrhea by stimulating the secretion of Cl⁻ ions into the intestinal lumen, followed by Na⁺ and water, leading to dehydration. Oral rehydration therapy (ORT), which consists of a solution of sugar (glucose) and Na⁺, takes advantage of the Na⁺/glucose cotransporter in the intestines. This cotransporter allows the reabsorption of Na⁺ and glucose, which then pulls water back into the body, preventing dehydration and death.