CB 002. updated Processes at membrane (1)

Processes at Membranes

Physiology Team Overview

Affiliated with New Giza University, School of Medicine. The Physiology Team focuses on understanding the fundamental processes at cellular membranes which are crucial for various physiological functions.

Objectives of the Lecture

• Define Key Terms: Provide clear definitions for channel and carrier proteins, including examples to illustrate their roles in transport across cell membranes.

• Understand Cell Voltage: Explain the mechanisms behind the negative plasma membrane resting voltage commonly observed in cells and predict how changes in the extracellular potassium concentration affect this resting voltage.

• Receptor Types: Differentiate between ionotropic and metabotropic cell surface receptors, presenting examples to elucidate their distinct signaling mechanisms.

Cell Membrane Structure and Composition

Components of Membrane:

• Phospholipids: Form the fundamental lipid bilayer of the membrane, characterized by hydrophobic (nonpolar) tails and hydrophilic (polar) heads, which dictate the fluidity and integrity of the membrane.

• Proteins: Include integral proteins that function as channels for transport and peripheral proteins that serve various roles including signaling and structural support.

• Carbohydrates: Present as glycoproteins and glycolipids, these components are essential for cell recognition and interactions with other cells.

Diffusion:

The process of diffusion is significantly influenced by the size and polarity of molecules. Small nonpolar molecules (such as oxygen and carbon dioxide) diffuse easily across membranes, while larger or polar molecules (such as ions and sugars) encounter greater resistance.

Factors Affecting Membrane Permeability

Key factors that influence the permeability of the membrane include:

• Lipid Solubility: Substances that are lipid-soluble can more readily pass through the membrane.

• Size and Shape: The physical dimensions of the molecules determine their ability to navigate through membrane channels.

• Temperature: Higher temperatures increase membrane fluidity and can enhance permeability.

• Membrane Thickness: Thinner membranes facilitate easier diffusion of substances.

Membrane Transport Mechanisms

Passive Transport (with gradient):

• Simple Diffusion: Movement of molecules due to thermal energy, occurring either through the lipid bilayer or through protein channels, depending on the size and polarity of the molecules.

• Facilitated Diffusion: This type of transport requires specific carrier proteins to help move certain molecules across the membrane without expending energy.

Active Transport (against gradient):

• Involves the use of energy to transport substances against their concentration gradient.

• Primary Active Transport: Directly uses ATP to pump molecules across the membrane, exemplified by the Na+-K+ ATPase pump.

• Secondary Active Transport: Relies on the electrochemical gradients established by primary active transport to drive the movement of other substances.

Simple and Facilitated Diffusion

Diffusion Through Cell Membrane:

• The rate of diffusion is influenced by factors such as the concentration gradient (driving force), the available surface area for diffusion, and the permeability properties of the membrane defined by Fick's Law of Diffusion, which quantitatively describes the flux of molecules across a membrane.

Ion Channels:

• These are specialized protein pores that allow ions to cross the membrane. Their opening and closing is controlled by various mechanisms, including:

  • Voltage-Gated Ion Channels: Open in response to changes in membrane potential, crucial for action potentials in neurons.

  • Ligand-Gated Ion Channels: Open in response to the binding of a specific ligand, allowing rapid signaling responses.

Carrier Proteins and Their Mechanisms

Facilitated Diffusion Carriers:

• Integral membrane proteins that typically have multiple transmembrane domains, allowing selective permeation for certain substrates. They can be categorized as:

  • Uniporters: Transport a single type of molecule across the membrane.

  • Symporters: Move two molecules in the same direction across the membrane.

  • Antiporters: Transport two molecules in opposite directions.

• For instance, glucose transport through glucose uniporters (GLUT) involves carrier-mediated transport where ligand binding prompts a conformational change in the transporter to facilitate movement.

Active Transport Systems

Primary Active Transport Example:

• The Na+-K+ pump is a critical Na+-K+ ATPase that actively transports three sodium ions out of the cell and two potassium ions into the cell for every molecule of ATP consumed, effectively maintaining the ionic gradient fundamental for resting membrane potential and cellular functions.

Secondary Active Transport Example:

• The Na+-glucose symporter utilizes the sodium gradient established by the Na+-K+ pump to transport glucose against its concentration gradient, highlighting the coupling of primary and secondary transport mechanisms.

Membrane Potential Basics

Resting Membrane Potential:

• It is primarily determined by the distribution of ions, especially potassium (K+), sodium (Na+), and chloride (Cl-). Typical values can range from -40 mV to -90 mV.

• The permeability of the membrane to these ions, particularly through K+ leak channels, plays a significant role in setting the resting membrane potential.

Key Equations:

• Nernst Equation: A fundamental equation used to calculate the equilibrium potential for an individual ion based on its concentration gradient between the inside and outside of the cell, aiding in the understanding of membrane potentials.

Receptor Types and Functions

Ionotropic Receptors:

• These are rapid acting, ligand-gated ion channels that directly permit ion flow into the cell upon receptor activation, facilitating fast synaptic transmission. Notable examples include nicotinic acetylcholine receptors, GABAA receptors, and glycine receptors.

Metabotropic Receptors:

• G protein-coupled receptors that typically have a slower onset of action than ionotropic receptors. They activate intracellular signaling pathways through second messengers. Examples include muscarinic acetylcholine receptors and adrenergic receptors, which modulate various physiological processes over longer time scales.

Summary of Membrane Transport Processes

• Passive Transport (Downhill): Includes simple diffusion and facilitated diffusion, both of which occur without energy expenditure, emphasizing the natural tendency of substances to move along their concentration gradients.

• Active Transport (Uphill): Requires energy from ATP, encompassing both primary and secondary active transport mechanisms, which underscore the abnormal distribution of ions and the necessity of transport proteins in maintaining cellular homeostasis.

References

• Guyton & Hall: Textbook of Medical Physiology.

• Lippincott Illustrated Reviews Physiology.