Biology Chapter on Membrane Properties

Biological Membranes - BIO 411

• SEM image shows a white blood cell (WBC), dyed red, destroying TB bacteria (yellow). The bacteria are engulfed by the WBC's cell membrane, rendering them harmless.

Learning Outcomes

• State the main components of biological membranes
• Identify the structural organization of membranes
• Relate structure and function of membranes
• Illustrate the current model of membranes
• Define and explain characteristics of membranes

Subtopics

• 2.1 Organization and fluidity of membrane components
• 2.2 Membrane excitation and special membrane structures
• 2.3 Membrane transport
• 2.4 Cell signaling and cell recognition

2.1 Organization and Fluidity of Membrane Components

• Lipids: Phospholipids + Glycolipids
• Proteins
• Phospholipid bilayer
• Plasma membrane

Plasma Membrane

• A microscopic membrane of lipids and proteins that forms the external boundary of a cell or encloses a vacuole, and regulates the passage of molecules in and out of the cytoplasm.

Plasma Membrane (PM)

• Phospholipid bilayer
• Hydrophobic regions of protein
• Hydrophilic regions of protein

Plasma Membrane (PM): Freeze Fracture Microscopy

• Extracellular layer
• Cytoplasmic layer
• Proteins inside the extracellular layer
• Proteins inside the cytoplasmic layer

General Characteristics of Plasma Membranes

• The plasma membrane is the boundary separating the living cell from its surroundings
• Membranes exhibit selective permeability (some substances cross more easily than others)
• Biological membranes provide separate compartments in the cell
• They are dynamic and fluid structures
• Membrane composition varies according to its site
• Amount and chemical properties of lipid & protein molecules affect membrane properties

Function of Plasma Membranes

• Compartmentalization (specialized internal activities)
• Scaffold for biochemical activities (effective interaction)
• Selectively permeable barrier
• Transporting solutes
• Responding to external signals (electrical & chemical)
• Intercellular interaction (adhesion and communication)

Fluid Mosaic Model

• Fluid (lipids) + Mosaic (protein)

History of Fluid Mosaic Model

• 1880 - Overton
• 1900 - Langmuir
• 1920 - Gorter and Grendel
• 1940 - Davson and Danielli
• 1960 - Robertson
• 1980 - Singer and Nicolson/ Unwin and Henderson
• 2000 -

Plasma Membranes

• Phospholipids are the most abundant lipid in a plasma membrane
• Phospholipids are amphipathic molecules, containing hydrophobic and hydrophilic regions
• The fluid mosaic model states that a membrane is a fluid structure with a "mosaic" of various proteins and phospholipids embedded in it

Components of Cell Membrane

• Lipids: phospholipid bilayer/phosphoglycerides, sphingolipids (amino+alcohol), glycolipids (CHO+lipids), cholesterols
• Carbohydrates: glycoprotein
• Proteins: transmembrane protein, interior protein network, peripheral protein, and glycoproteins

Fluid Mosaic Model (Singer & Nicolson, 1972)

• Polar hydrophilic heads
• Nonpolar hydrophobic tails

Fluid Mosaic Model

• Plasma membrane is composed of both lipids and globular proteins
• Membrane proteins are not very soluble in water
• Cholesterol molecules embedded in the membrane affect the close packing of the hydrophobic tails of the phospholipids and therefore the fluidity of the membrane by disturbing Van der Waals interactions

Fluidity of PM

• Unsaturated hydrocarbon tails with kinks
• Saturated hydrocarbon tails

Membrane Lipids

• Types of membrane lipids
• Phospholipid bilayer/phosphoglycerides
• Sphingolipids (amino+alcohol)
• Glycolipids (CHO+lipids)
• Cholesterols
• Phospholipids form the backbone of biological membranes
• The amount of lipid varies from 20% to 78% according to the site of the membrane
• Phospholipid molecules can self organize to form stable membranes

Function of Lipid Component

• Physical state of a membrane
• Influence the activity of particular membrane proteins
• Precursors for highly active chemical messenger
• Continuous interconnection, unbroken structures
• Facilitate the regulated fusion or budding of membranes
• Maintain the proper internal composition of a cell
• Able to self-assemble (e.g., liposomes)

Phospholipid Bilayer

• Phospholipid has two fatty-acid chains attached to its backbone
• One end is strongly nonpolar while the other is strongly polar
• Polar head oriented toward water (hydrophilic)
• Nonpolar tails oriented away from water (hydrophobic) - amphipathic lipids
• Bilayer structure is stable because of water's affinity for hydrogen bonding

Amphipathic Lipids

• Amphipathic lipid molecule consisting of: polar head and hydrophobic fatty acid tail
• When suspended in aqueous solution they form stable micelle structures

PM Component: Phospholipids

• Lateral movement (~107 times per second)
• Flip-flop (~once per month)

PM Component: Cholesterol

• Cholesterol within the animal cell membrane
• How does cholesterol affect the fluidity of the membrane

Membrane Proteins

• Major types: transmembrane proteins, interior protein network, peripheral protein, glycoproteins

Integral/Transmembrane Proteins

• Embedded within the membrane
• May extend through the membrane and project at both surfaces
• Some only extend through one membrane layer and only project on one side

Peripheral Proteins-Surface

• Located on the surface of the PM
• Loosely bound and can be removed with mild detergent

Integral/Transmembrane Proteins

• Hydrophilic end interacts with water-soluble substances
• Large proteins contain interior channels for passage through the PM
• Single-pass anchors
• Multiple-pass channels and carriers
• Pores

Peripheral Proteins-Surface

• Functions:

• Form fibrillar networks-membrane skeleton attachments to the cytoskeleton

• Provide anchor for the integral proteins

• Enzymes

• Transmit transmembrane signals

• Lipid-anchored proteins

• As receptors

• Cell adhesion proteins

Functions of Membrane Proteins

• Transporter function
• Enzyme function
• Cell surface receptor function
• Cell surface identity marker function
• Cell adhesion function
• Attachment to cytoskeleton function

Membrane Carbohydrates

• Linked to lipids (glycolipids) or proteins (glycoproteins—90%)
• Roles: mediating interactions between cell and its environment, sorting membrane proteins to different cellular compartments, antigenic markers (ABO blood groups)

Becker Page Membrane Excitation & Special Membrane Structures (End of Today's Lecture)

• Subtopics:
  • Organization and fluidity of membrane components
  • Membrane excitation and special membrane structures
  • Membrane transport
  • Cell signalling and cell recognition

What Will Be Covered

• Neurons
• Na/K pump
• Saltatory conduction
• Ion distribution across membrane Special membrane structures: adherent junction, tight junction, gap junction, plasmodesmata

CNS, PNS & Neurons

• Nervous system = CNS + PNS

• CNS command center

• PNS processing center; collects information and carries out responses

• 2 types of cells in nervous system: neurons and glial cells

• Neuronal highway connecting PNS to CNS (interneurons)

• Sensory neurons (PNS)

• Motor neurons (PNS)

Basic Neuron Design

• Cell body
• Nucleus
• Dendrites
• Axon hillock
• Axon
• Myelin sheath
• Node of Ranvier
• Synapses

The Mechanism of Nerve Impulse Transmission

• Membrane potential arises from the interaction between membrane and transmembrane proteins in the plasma membrane
• Basis of electrical potential difference across the plasma membrane

The Inside of Cell More Negatively Charged

• Excess anions inside, excess cations outside
• Intracellular fluid
• Extracellular fluid
• Plasma membrane

Major League Players

• Na/K Pump (pumps 2K+ into cell for 3Na+ pumped out)
  • Establishes & maintains concentration difference[K+]i; [Na+]o
• Ion Channels (membrane proteins forming pores, allowing diffusion of ions)
  • More numerous and higher permeability for K+

Major Forces Acting on Ions

• Electrical potential (unequal distribution of charges across membrane)
• Chemical force (unequal concentrations of ions across membrane)

Read on Resting Membrane Potential (End of Today's Lecture)

The Mechanism of Nerve Impulse Transmission

• Learning Outcomes:
  • Identify ions involved in nerve impulse transmission and their relative concentration inside and outside the neuron
  • Describe the production of the resting potential
  • Explain how the action of voltage-gated channels produces an action potential

The Mechanism of Nerve Impulse Transmission

• When neurons are not stimulated, it maintains resting potential (-40 to -90mV; use -70mV (-ve inside vs outside))
• Formation of resting potential (equilibrium between 2 forces) caused by 2 factors
• Resting potential arises from the interaction between membrane and proteins in plasma membrane, forming the basis of electrical potential across the plasma membrane.

Major League Players

• Na+/K+ Pump (pumps 2K+ INTO cell for 3Na+ pumped OUT
• Ion Channels (membrane proteins forming pores; allows diffusion of ions) More numerous & higher permeability for K+

Resting Potential

• Arise due to Na/K pump and differential permeability of membrane to Na+ and K+, due to ion channels.
• Concentration gradient created by the pump is significant
• K+ inside is higher; diffuse out through open channels
• Membrane is NOT permeable to -ve ions (organic phosphates, proteins, amino acids)

Resting Potential

• Not able to counterbalance: buildup of +ve ions outside, -ve ions outside
• Electrical potential is an attractive force pulling K+ back into the cell
• Balance between electrical and diffusional forces leads to equilibrium potential

Resting Potential

• Nernst Equation Ex = 58 mV log ([K+]out / [K+]in) (Describes relationship between membrane potential and ion concentration)
• Goldman Equation Em=(RT/F)ln(PK[K+]out +PNa[Na+]out + PC1[Cl-]in/PK[K+]in +PNa[Na+]in+PC1[Cl-]out) (Describes combined effects of ions on membrane potential)

Read Becker Page 367-379 (on Graded Potentials and Action Potentials) (End of Today's Lecture)

THE MECHANISM OF NERVE IMPULSE TRANSMISSION

• Neurons are unique as sudden temporary disruptions to resting membrane potential occur in response to stimuli
• Two types of changes can be observed: graded potentials and action potentials

Graded Potentials

• Fluctuations in potentials; able to reinforce or negate each other
• Mechanisms: ligand-gated channels, depolarization, and hyperpolarization

Ligand Gated Channels

• Temporary binding of ligands (hormones + neurotransmitters) changes the conformation of membrane receptor proteins of channels

Depolarization & Hyperpolarization

• Effect of permeability changes; measured as depolarization or hyperpolarization
• Depolarization: Vm becomes > +ve (e.g., change from -70mV to -65mV)
• Hyperpolarization: Vm becomes > -ve (e.g., change from -70mV to -75mV)
• Depolarizing and hyperpolarizing effects can combine to amplify or reduce their effects

Recap

• Classes of ion channels discussed so far: ligand-gated ion channels and voltage-gated ion channels (action potentials)

The Action Potential

• "All-or-none": always the same size
• Either not triggered at all (too little depolarization/membrane is refractory) or triggered completely

The Mechanism of Nerve Impulse Transmission

• Action potentials exist when depolarization reaches and exceeds threshold
• Caused by voltage-gated channels (either Na+ or K+ voltage-gated channels)
• Used to establish action potential in neurons

The Action Potential

• 4 phases: Resting phase, rising phase, top of curve, and falling phase\

The Action Potential phases 1-4

• Resting phase: Voltage-gated ion channels are closed; partial diffusion of K+
• Rising phase: Voltage-gated Na+ channels OPEN; influx of Na+ into axon; rapid depolarization (spike)
• Top of curve: Voltage-gated Na+ channels CLOSE; no more Na+ enters axon; Voltage-gated K+ channels OPEN
• Falling phase: Repolarization occurs; K+ diffuses out from axon; Hyperpolarization occurs before original resting potential is restored

Nature of Action Potentials

Action potential upstroke (depolarization) downstroke (repolarization) threshold potential resting membrane potential graded potential hyperpolarization

Action Potential Exercise

• Matching numbers to events in the graph.

Propagation of Action Potentials

• How action potentials are established
• How action potentials are propagated

Propagation of Action Potentials

• Factors affecting impulse transmission (more or less nerve being stimulated, type of nerve, differing speed depending on axon diameter/strength of stimulus)
• Achieved through saltatory conduction (~120m/sec)

Propagation of Action Potentials

• Thinking of propagation of action potentials as dominos
• Myelinated axon provides the domino effect, making saltatory conduction possible

Saltatory Conduction

• Rapid transmission of a nerve impulse along an axon, resulting from the action potential jumping from one node of Ranvier to another, skipping the myelin-sheathed regions of the membrane

Myelinated Axon

• Myelination (in central and peripheral nervous systems)
• The myelin sheath is provided by oligodendrocytes and Schwann cells
• Myelin is insulating, preventing ions from passing over the membrane (80% lipid and 20% protein)

Myelination

• How myelin sheath is formed

Inter Neural Transmission

• Communication between neurons achieved through transmission of signals using neurotransmitters
• Gap junction forms the synapse between two neurons

Inter Neural Transmission

• SYNAPTIC CLEFT = The void
• SYNAPTIC VESICLES = The vehicle
• NEUROTRANSMITTERS = Ach, amino acids, epinephrine, norepinephrine, dopamine, serotonin

Inter Neural Transmission

• Depolarization opens Ca+ channel; Ca+ influx into the terminal knob-neural transmitter (NT) vesicle fuses with PM
• NT released into the synapse, binds to postsynaptic receptors, triggers action potentials (influx of Na+) or inhibits action potentials (influx of Cl-) in adjacent neuron

End of Today's Lecture

Subtopics

• Organization and fluidity of membrane components
• Membrane excitation and special membrane structures
• Membrane transport
• Cell signaling and cell recognition

2.3 Learning Outcomes

• Identify, explain, provide examples, and state the importance of the different types of membrane transport
• Distinguish passive (no energy investment) from active (energy investment) transport
• Explain the mechanism involved in different types of active transport
• Relate membrane components (with transport types) across the membrane

What is the Main Characteristic of Plasma Membranes?

• Selective permeability

Membrane Transport

• Cells require specific chemicals for life processes and need to dispose of waste products
• Small molecules (O2, CO2, ethanol) can diffuse across the membrane at various rates, depending on their ability to enter the hydrophobic interior of the membrane bilayer.
• Ions require transport across membrane

Membrane Transport

• Lipid bilayer is impermeable to: ions (K+, Na+, Ca2+, Cl-, HCO3−), small hydrophilic molecules (glucose), macromolecules (proteins and RNA).

Membrane Transport

• Permeability of a molecule through a membrane depends on the interaction of that molecule with the hydrophobic core of the membrane
• Hydrophobic molecules easily dissolve in the lipid bilayer and cross easily
• Ions and polar molecules pass through the membrane with difficulty
• Proteins can assist in regulating the transport of ions and polar molecules across the membrane

Types of Membrane Transport

• Diffusion
• Facilitated diffusion
• Osmosis
• Bulk transport
• Active transport

Overview of Membrane Transport Systems

• Uniport (one solute transported)
• Passive Transport 　- Simple Diffusion 　- Facilitated Diffusion 　　- Rapid diffusion down a concentration gradient 　　- Saturable transporter 　　- Specific 　- Gated Ion Channels
• Active Transport 　- Primary active transporters 　- Secondary active transporters: Cotransport (transport of one solute is coupled to transport of another) 　　　• Symport 　　　• Antiport

Passive & Active Transport

• Passive: molecules move down concentration gradient; no energy required; e.g., osmosis and diffusion
• Active: movement of molecules against concentration gradient; energy required

1º Active Transport

• Proteins in the membrane act as pumps; move ions/molecules against their concentration gradients using ATP
• Saturates when substance reaches high concentrations due to lack of available protein

1º Active Transport: Na-K-ATPase Pump

• Ratio of transport = 3 Na:2 K
• Steps in cycle.

Importance of the Na-K-ATPase Pump

• Establishing a net charge across the plasma membrane with the interior of the cell being negatively charged with respect to the exterior
• Preparing nerve and muscle cells for the propagation of action potentials (leading to nerve impulses and muscle contraction)
• Maintaining osmotic balance (ensuring cells don't swell and burst)

Active Transport

• The sodium-potassium pump actively maintains the gradient of sodium (Na+) and potassium (K+) ions across the membrane
• Typically, an animal cell has higher concentrations of K+ and lower concentrations of Na+ inside the cell.
• The sodium-potassium pump uses the energy of one ATP to pump three Na+ ions out and two K+ ions in.

Active Transport: Primary and Secondary

• Primary: Directly derived from ATP breakdown
• Secondary: Secondary derived from stored ionic concentration differences
• Type: Symport/antiport

Active Transport: Ca2+ ATPase Pump

• Two types of Ca2+ ATPase pumps
  • Plasma Membrane Ca2+ ATPase (PMCA)
  • Sarcoplasmic Reticulum Ca2+ ATPase (SERCA)

1º Active Transport: Sarcoplasmic Reticulum (SR) Ca2+ ATPase

• Locatiion in the SR (endoplasmic reticulum) of muscle cells.
• Transfers Ca2+ from cytoplasm to SR lumen.
• Hydrolysis of ATP
• After muscle contraction Ca2+ is pumped back into the sarcoplasmic reticulum by a Ca2+ ATPase that uses energy from ATP

1º Active Transport: PM Ca 2+ ATPase

• Plasma membrane Ca2+ ATPase (PMCA) is a transport protein in the plasma membrane of cells, removes Ca2+ from the cell
• Vital for regulating Ca2+ in eukaryotic cells, with large transmembrane gradients (ICF ECF 10-20 mM:150 mM)
• Drives the entry and the propagation of cell signaling

1° Active Transport: Proton (H+) Pumps (H+-ATPase)

• Parietal cells of the stomach use this pump to move protons (H+) into gastric juice (pH close to 1)
• Plants, bacteria, and fungi employ proton pumps to actively transport H+ out of the cell
• Proton pumps in mitochondria and the thylakoids of chloroplasts concentrate H+ behind membranes, these store energy

2° Active Transport (Cotransport)

• Definition: Energy from ATP hydrolysis used to generate a gradient of another solute; its movement "down" its concentration gradient used to drive transport of a different solute against its concentration gradient
• Cotransport is a type of 2° active transport
• Example:
• Symport: different solutes transported in the same direction
• Antiport: different solutes transported in opposite directions

2º Active Transport

• Cotransporters restore [ion] using ATP

2º Active Transport

• Examples of cotransport: glucose and Na+ (in human gut epithelial cells), amino acids, sugars (in plants) and ribose (in E.coli)

Osmosis

• Osmosis is passive transport of water through a selectively permeable membrane, between two solutions with differing concentrations.
• Hypertonic solution (higher solute concentration): higher concentration of solutes; lower water concentration
• Hypotonic solution (lower solute concentration): lower concentration of solutes; higher water concentration
• Isotonic solution: equal solute concentrations; same relative water concentration

Osmosis

• Osmotic concentration = concentration of all solutes in a solution
• Hyper-osmotic = solution of high solute concentration
• Hypo-osmotic = solution of low solute concentration
• Iso-osmotic = solutions of equal concentration

Case Study: Osmosis

• Two solutions with differing concentrations are separated by a membrane that allows water to pass through but not solutes
• Hypertonic solution has lower water concentration than hypotonic solution; water molecules move from the hypotonic solution to the hypertonic solution
• Osmosis continues until solutions are isotonic

Osmosis

• Organism without rigid cell walls experience osmotic shifts (hypertonic or hypotonic environments) and need osmoregulation
• Example: Paramecium has contractile vacuoles

Osmosis (Human and plant cells)

• Cells in an isotonic environment (e.g. marine invertebrates/most terrestrial animals do not experience osmotic fluctuations)
• Cells in a hypertonic environment (e.g., Paramecium): higher external solute concentration, water moves out of the cell
• Cells in a hypotonic environment (e.g., plant cells): lower external solute concentration, water moves into the cell

Bulk Transport

• Endocytosis (enveloping food) 　　- Phagocytosis: particulate (solid) material 　　- Pinocytosis: liquid material 　　- Receptor-mediated endocytosis: specific molecules
• Exocytosis (discharge of material from vesicles)
  • Vesicles produced by Golgi apparatus

Bulk Transport: Phagocytosis

• Pseudopodium surrounds and engulfs a substance in the extracellular fluid
• Forms a food vacuole
• Materials are digested within cell

Bulk Transport: Pinocytosis

• Plasma membrane folds inward forming small vesicles

Receptor-Mediated Endocytosis

• Extracellular substances (ligands) bind to specific receptors, especially near coated pits.
• This induces formation of a vesicle.

Receptor-Mediated Endocytosis: Clathrin Coated Pits

• A type of endocytosis using clathrin-coated pits

Receptor-Mediated Endocytosis

• enables a cell to acquire bulk quantities of specific materials that may be in low concentrations in the environment
• Human cells use this process for absorbing cholesterol.
• Cholesterol travels in the blood in low-density lipoproteins (LDL), which bind to LDL receptors, and enter the cell by endocytosis

Endocytosis & Exocytosis

• Process of bringing & releasing materials in/out to and from the cell.
• Steps of Receptors binding a signal molecule; Ligand-receptor migrates to coated pit; Endocytosis; Vesicle loses clathrin coat; Receptors and ligands separate

Subtopics

• Organization and fluidity of membrane components
• Membrane excitation and special membrane structures
• Membrane transport
• Cell signaling and cell recognition

Cell Communication & Signaling

• Importance of cell-to-cell contact in multicellular organisms
• Communication often achieved through cell signal transduction
• Exogenous molecule received by a cell, converted into a response.
• Reception relay, transduction (protein modification and amplification), and response

Cellular Activities

• Transcription
• Survival
• Protein synthesis
• Movement
• Cell death
• Metabolic change

Cell Signaling Mechanisms

• Paracrine signaling (local)
• Synaptic signaling
• Endocrine signaling (distant)

Paracrine Signaling (Local)

• Local chemical messengers are targeted to specific receptors.
• Often includes growth factors and neurotransmitters between neurons

Paracrine Signaling (localized)

• Target cell is close to the signal-releasing cell The signal chemical is broken down too quickly to be carried to other parts of the body.

Endocrine Signaling (distant)

• Specialized cells release hormones into blood vessels; hormones move to distant target cells and elicit responses.

Cell-to-Cell Signaling

• Signaling can be more direct with cell-to-cell contact, involving gap junctions or plasmodesmata.
• Cell-surface contacts receptor protein specificity
• Examples of cytokines to increase immune response

Receptor Proteins & Signal Transduction

• Ion channel receptors (ligand-gated protein channels)
• A protein pore in a membrane opens; response to binding of a signal molecule
  • Ex: neurotransmitter acetylcholine (Ach) opens channels, letting Na+ flood into cell, changes the electrical charge

Cell Signaling via Signal Transduction Pathway

• Cascade of events triggered when a ligand binds to a receptor protein, leading to a cellular response

The 3 Stages of Cell Signaling

Reception: ligand molecule is recognized by a single receptor within the cell membrane Transduction: leads to a shape change in the receptor, interacting with other intracellular molecules Response: cellular activity (enzyme catalysis, cytoskeleton rearrangement, or specific gene activity)

Receptor Types

• Extracellular messengers (amino acids, hormones, neurotransmitters, steroids, eicosanoids, proteins and polypeptides)
• Receptors (G proteins, receptor protein tyrosine kinases RTKs, ligand-gated channel, steroid hormone receptors, and B and T cell receptors)

G Protein Coupled Receptor Structure

• Has 7 transmembrane α-helices
• Possesses a site for a receptor molecule
• A specific example of G-protein cellular response- Fight or flight responses
• 1 signal triggers a multiple amplified response

Receptor G-Protein & Signal Transduction System

• G-Protein receptors bind to GTP/GDP instead of ATP
• Convert between active and inactive forms; a signal molecule binding to a receptor triggers a conformational change; the inactive G-protein now binds GTP, becoming active, and the active G-protein- stimulates other inactive enzymes

G-Protein

• Has its GTP hydrolyzed
• Inactivates the G-protein

G Protein and 2nd Messengers

• Second messengers are small substances that activate or inactivate specific proteins
• Signal molecules (hormone epinephrine) lead to activation of membrane-bound inactive enzyme adenyl cyclase
• ATP is converted to cyclic AMP (cAMP) which leads to cellular processes

Epinephrine for Glycogen Breakdown

• Steps in the cascade

Cholera Toxin

• Vibrio cholerae toxin prevents conversion of GTP (active) to GDP (inactive)
• G-protein remains active; cAMP remains active, causing diarrhea

Specific Examples of G-Protein Cellular Responses

• Mouse embryos lacking one G-protein show no blood vessel development
• Some human embryos w/o G-proteins exhibit decreased senses (especially vision and smell)

Tyrosine Kinase Receptors

• Receptor proteins that have kinase activity, adding a PO4 group to tyrosine residues of inactive proteins, making them active
• Tyrosine Kinases elicit cellular responses, like growth factors, stimulating cell division and growth via tyrosine-kinase activation

Non-membrane Bound (cytoplasmic-intracellular) Receptors

• Signal molecules (usually lipid-soluble) diffuse through the membrane and binding to an intracellular receptor protein initiates a cellular response (e.g., steroid hormones)
• Signal molecules bind to receptor proteins

Steroid Hormones (Intracellular Response)

• Steps in the mechanism, including hormone binding, receptor complex formation, DNA interaction, transcription, mRNA formation, and protein translation

Calcium Ions as Second Messengers

• Cells maintain low cytosolic Ca2+ levels (10-7 M) via active transport (Ca2+ pumps) in the cytoplasm, in contrast with high Ca2+ levels in other organelles (ER and mitochondria; 10,000x greater)
• Ca2+ functions as a second messenger; increase in cytoplasmic Ca2+ triggers various cellular responses, such as muscle contractions and neurotransmitter release

Mechanisms That Maintain Low Calcium in the Cytosol

• Calcium channels in PM and ER membranes are kept closed.
• ATP-driven Ca2+ pumps transport it out of cytosol.
• Calcium ions as the second messenger.
  • IP3 opens the calcium gate to release calcium into the cytosol—muscle contraction, cell division, secretion, fertilization, synaptic transmission, metabolism, transcription, and cell movement
• Calcium-binding protein-calmodulin

1° Active Transport: PM Ca2+ ATPase

• The plasma membrane, Ca2+ATPase(PMCA), removes Ca2+ from the cell via the plasma membrane.
• Vital for regulating Ca2+ in eukaryotic cells; large transmembrane gradients.
• Main regulators of intracellular Ca2+ concentration: PMCA and sodium calcium exchanger

1º Active Transport: Proton (H+) Pumps

• Parietal cells in the stomach use proton pumps to move protons (H+) into gastric juice.
• In plants, bacteria, and fungi, proton pumps actively transport H+ out of the cell.
• Protons pumps in the cristae of mitochondria, and thylakoids, concentrate H+ behind the membranes

2º Active Transport (Cotransport)

• Energy is derived secondarily from energy stored as differences in ionic concentrations across a membrane. 
• Energy from electrochemical gradient
• Two types: 　　-Symport- moves multiple substances in the same direction. 　　-Antiport- moves multiple substances in opposite directions

End of Topic 2

Test your knowledge on amphipathic molecules, cations, and the permeability of the lipid bilayer. This quiz covers critical concepts related to cellular membranes and the nervous system, including ion channels and neuronal signaling. Prepare for questions on the Na/K pump and types of junctions in cells.