Active Membrane Transport and Membrane Potential in Cells

Cells: The Living Units

Introduction

Cells are the fundamental units of life, responsible for carrying out all vital physiological processes. One of the essential functions of cells is to regulate the movement of substances across their plasma membranes, maintaining internal homeostasis and enabling communication with their environment.

Active Membrane Transport

Overview of Active Transport

Active membrane transport processes are mechanisms by which cells move substances across their plasma membranes against concentration gradients, requiring energy input, usually in the form of ATP. These processes are crucial for maintaining concentration gradients of ions and other molecules, which are essential for cellular function.

• Active transport: Direct movement of solutes using energy.

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

Active transport is necessary when:

• The solute is too large for channels.

• The solute is not lipid-soluble.

• The solute cannot move down its concentration gradient.

Types of Active Transport

• 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

In primary active transport, the hydrolysis of ATP causes a conformational change in a transport protein, allowing it to move solutes (such as ions) across the membrane against their concentration gradients.

• Examples of primary active transport pumps: Calcium pumps, hydrogen (proton) pumps, and the sodium-potassium (Na+-K+) pump.

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

• Most studied active transport pump.

• Functions as an enzyme that pumps 3 Na+ ions out of the cell and 2 K+ ions into the cell per ATP molecule hydrolyzed.

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

Mechanism:

1. Na+ binds to the pump from the cytoplasm.

2. ATP is hydrolyzed, causing a conformational change.

3. Na+ is released outside the cell; K+ binds from the extracellular fluid.

4. The pump returns to its original shape, releasing K+ inside the cell.

Equation:

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

Importance: Maintains electrochemical gradients essential for nerve impulse transmission and muscle contraction.

Inhibitors: Certain toxins (e.g., oleander tree toxin, digitalis from foxglove) can inhibit the Na+-K+ pump, affecting heart and nerve function.

Secondary Active Transport (Cotransport)

Secondary active transport uses the energy stored in ionic gradients created by primary active transport to move other substances against their own gradients. This process requires carrier proteins (solute pumps) that bind specifically and reversibly to the substances being transported.

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

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

For example, the low intracellular Na+ concentration maintained by the Na+-K+ pump allows Na+ to flow back into the cell, often bringing glucose or amino acids with it via symporters.

Vesicular Transport

Overview

Vesicular transport involves the movement of large particles, macromolecules, and fluids across the plasma membrane in membranous sacs called vesicles. This process requires cellular energy, usually ATP.

• Endocytosis: Transport into the cell.

• Exocytosis: Transport out of the cell.

• Transcytosis: Moving substances across, into, and then out of the cell.

Types of Endocytosis

Type	Main Features	Example
Phagocytosis	"Cell eating"; cell engulfs large particles using pseudopods, forming a phagosome.	Macrophages engulfing bacteria.
Pinocytosis	"Cell drinking"; cell engulfs extracellular fluid and dissolved solutes in small vesicles. Nonspecific process.	Absorption of nutrients in the small intestine.
Receptor-mediated endocytosis	Specific molecules bind to receptors in clathrin-coated pits, allowing selective uptake.	Uptake of LDL cholesterol, iron, insulin.

Phagocytosis

• Used by specialized cells (e.g., macrophages, neutrophils).

• Involves formation of pseudopods to engulf particles.

• Phagosome fuses with lysosome for digestion.

Pinocytosis

• Non-selective uptake of extracellular fluid.

• Important for nutrient absorption and sampling the environment.

• Membrane components are recycled.

Receptor-Mediated Endocytosis

• Highly selective; involves specific receptors and clathrin-coated pits.

• Allows uptake of specific substances (e.g., hormones, vitamins, viruses).

• Some pathogens exploit this pathway to enter cells.

Exocytosis

Exocytosis is the process by which cells expel materials in vesicles that fuse with the plasma membrane. This process is triggered by cell-surface signals or changes in membrane voltage.

• Used to secrete hormones, neurotransmitters, mucus, and cellular wastes.

• Involves SNARE proteins that mediate vesicle docking and fusion.

• Disruption of exocytosis can have physiological effects (e.g., botulinum toxin blocks neurotransmitter release).

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 such as neurons and muscle cells.

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

• Typical RMP values range from -50 to -100 mV (inside of the cell is negative relative to the outside).

• Cells with a charge are said to be polarized.

Role of Potassium (K+) and Sodium (Na+)

• K+ diffuses out of the cell through leakage channels, making the inside more negative.

• Negatively charged proteins remain inside the cell, contributing to the negative charge.

• Na+ is attracted to the inside of the cell but the membrane is less permeable to Na+ than K+.

• The electrochemical gradient for K+ sets the RMP; Na+ can influence RMP if it enters the cell.

Typical RMP: Around -80 mV in most cells.

Maintenance of Membrane Potential

• The Na+-K+ pump maintains the gradients by continuously ejecting Na+ and bringing K+ back in.

• Steady state is achieved when the rate of Na+ entry equals the rate of Na+ pumping out.

• Excitable cells (neurons, muscle cells) can "upset" this steady state by opening gated channels, leading to action potentials.

Summary Table: Sodium and Potassium Ion Concentrations

Ion	Concentration Outside Cell	Concentration Inside Cell
Na+	High	Low
K+	Low	High

Key Point: Sodium ion concentrations are high outside the cell relative to inside the cell; potassium ion concentrations are high inside the cell relative to outside.

Additional info: The maintenance of these gradients is vital for processes such as nerve impulse transmission, muscle contraction, and secondary active transport of nutrients.