Active Membrane Transport and Membrane Potential in Cells

Cells: The Living Units

Introduction to Cell Membrane Transport

Cells maintain concentration gradients of various chemicals across their plasma membranes, which is essential for cellular function. These gradients represent potential energy that cells utilize to perform vital processes, especially in excitable tissues such as nerves and muscles.

• Active membrane transport requires energy (ATP) to move solutes across the plasma membrane.

• Two major types: Active transport and Vesicular transport.

• Active transport is necessary when solutes are too large for channels, not lipid soluble, or unable to move down their concentration gradient.

Active Transport

Types of Active Transport

Active transport mechanisms move substances against their concentration gradients, requiring cellular energy.

• Primary active transport: Energy comes directly from ATP hydrolysis.

• Secondary active transport: Energy is obtained indirectly from ionic gradients created by primary active transport.

Primary Active Transport

Primary active transport uses ATP to change the shape of transport proteins, allowing solutes (such as ions) to be pumped across the membrane.

• Examples of pumps: Calcium pumps, Hydrogen (proton) pumps, Sodium-potassium (Na+-K+) pumps.

• These pumps are essential for maintaining cellular ion balance.

Sodium-Potassium Pump (Na+-K+ ATPase)

The sodium-potassium pump is the most studied active transport pump. It is an enzyme that pumps 3 Na+ ions out of the cell and 2 K+ ions into the cell, maintaining essential gradients.

• Located in all plasma membranes, especially active in excitable cells (neurons and muscle cells).

• Functions as an antiporter, moving Na+ and K+ in opposite directions.

• Maintains electrochemical gradients (concentration and electrical differences).

• Essential for muscle contraction and nerve impulse transmission.

Equation:

$3\,\mathrm{Na}^+_{\text{(in)}} + 2\,\mathrm{K}^+_{\text{(out)}} + \mathrm{ATP} \rightarrow 3\,\mathrm{Na}^+_{\text{(out)}} + 2\,\mathrm{K}^+_{\text{(in)}} + \mathrm{ADP} + \mathrm{P}_i$

Inhibitors: Substances such as oleander tree toxin and digitoxin (foxglove) can inhibit the Na+-K+ pump, affecting cardiac and neural function.

Secondary Active Transport

Secondary active transport relies on ion gradients established by primary active transport. Carrier proteins (solute pumps) bind specifically and reversibly to substances being moved.

• Symporters: Transport two different substances in the same direction.

• Antiporters: Transport one substance into the cell while transporting another out.

• Energy stored in ion gradients (e.g., low intracellular Na+ concentration) is used to drive the transport of other solutes, such as sugars and amino acids.

Example: The Na+-glucose symporter uses the Na+ gradient to transport glucose into cells.

Vesicular Transport

Overview of Vesicular Transport

Vesicular transport moves large particles, macromolecules, and fluids across membranes using membranous sacs called vesicles. This process requires cellular energy, usually ATP.

• Includes endocytosis (into the cell) and exocytosis (out of the cell).

• Transcytosis refers to moving substances from one area of the cell to another.

Types of Endocytosis

Endocytosis is the process by which cells take in substances by engulfing them in vesicles. There are three main types:

Type	Description	Key Features	Example
Phagocytosis	"Cell eating"; engulfment of large particles	Uses pseudopods; forms phagosome; selective	Macrophages engulf bacteria
Pinocytosis	"Cell drinking"; uptake of extracellular fluid	Non-selective; forms small vesicles	Absorption of nutrients in small intestine
Receptor-mediated endocytosis	Specific uptake of molecules via receptors	Highly selective; uses clathrin-coated pits	Uptake of LDL, insulin, viruses

Phagocytosis

Phagocytosis involves the formation of pseudopods that surround and engulf solid particles, forming a phagosome. This process is used by specialized cells such as macrophages and certain white blood cells.

• Phagocytic cells move by amoeboid motion.

• Phagosomes often fuse with lysosomes for digestion.

Pinocytosis

Pinocytosis is the non-selective uptake of extracellular fluid and dissolved solutes. The plasma membrane folds inward to form vesicles containing fluid.

• Main method for nutrient absorption in the small intestine.

• Membrane components are recycled back to the plasma membrane.

Receptor-Mediated Endocytosis

This process involves the selective uptake of specific molecules that bind to receptors in clathrin-coated pits. The vesicle is internalized along with the bound molecule.

• Examples: enzymes, low-density lipoproteins (LDL), iron, insulin.

• Some pathogens exploit this mechanism to enter cells (e.g., viruses, diphtheria toxin).

Exocytosis

Exocytosis is the process by which cells expel materials in vesicles. It is usually triggered by cell-surface signals or changes in membrane voltage.

• Substances exocytosed include hormones, neurotransmitters, mucus, and cellular wastes.

• Involves docking of vesicle SNARE proteins with target SNAREs on the membrane.

Clinical relevance: Botulinum toxin blocks exocytosis of acetylcholine, while black widow spider venom causes uncontrolled exocytosis of acetylcholine at neuromuscular junctions.

Membrane Potential

Resting Membrane Potential (RMP)

The resting membrane potential is the electrical potential energy produced by the separation of oppositely charged particles across the plasma membrane. It is essential for the function of excitable cells.

• Voltage occurs only at the membrane surface; the rest of the cell and extracellular fluid are neutral.

• Typical membrane voltages range from -50 to -100 mV (inside is more negative).

• Cells with a charge are said to be polarized.

Role of Potassium (K+) in RMP

K+ diffuses out of the cell through leakage channels down its concentration gradient, while negatively charged proteins remain inside, making the cytoplasmic side more negative.

• K+ is pulled back by the negative interior (electrical gradient).

• RMP is established when the drive for K+ to leave is balanced by its drive to stay.

• Most cells have an RMP around -80 mV.

Equation:

$E_{K^+} = \frac{RT}{zF} \ln \left( \frac{[K^+]_{\text{out}}}{[K^+]_{\text{in}}} \right)$

Additional info: This is the Nernst equation for potassium, describing its equilibrium potential.

Role of Sodium (Na+) in RMP

Na+ also affects RMP, as it is attracted to the negative interior. However, the membrane is more permeable to K+, so K+ is the primary influence on RMP.

• If Na+ enters the cell, it can bring RMP up to -70 mV.

• Cl- does not influence RMP significantly because its gradients are balanced.

Maintenance of Electrochemical Gradients

The Na+-K+ pump maintains electrochemical gradients by continuously ejecting Na+ and bringing K+ back into the cell. The steady state is maintained because the rate of active pumping equals the rate of diffusion.

• Excitable cells (neurons and muscle cells) can intentionally open gated Na+ and K+ channels to "upset" the steady state, allowing for action potentials.

Summary Table: Comparison of Endocytosis Types

Type	Mechanism	Specificity	Example
Phagocytosis	Engulfment of large particles by pseudopods	Selective	Macrophages ingest bacteria
Pinocytosis	Uptake of extracellular fluid	Non-selective	Intestinal absorption
Receptor-mediated	Binding to specific receptors in coated pits	Highly selective	LDL uptake, virus entry

Key Concepts and Definitions

• Active transport: Movement of substances against their concentration gradient using energy.

• Vesicular transport: Movement of large particles or fluids via vesicles.

• Electrochemical gradient: Combined effect of concentration and electrical gradients on ion movement.

• Resting membrane potential (RMP): The voltage difference across the plasma membrane in resting cells.

• Symporter: Carrier protein that moves two substances in the same direction.

• Antiporter: Carrier protein that moves substances in opposite directions.