Exam 1 Studyguide PDF

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Exam 1 Studyguide...

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Membrane Dynamics 1.

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Review the general structure of the plasma membrane. Identify the basic parts of a phospholipid, and types of membrane proteins. 

Plasma Membrane: This is the boundary between the cell and its environment. Its function is to regulate what enters and exits the cell. It is important that cells must maintain an appropriate number of molecules inside in order for them to function.

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Structure of Plasma Membrane: This is composed of a PHOSPHOLIPID BILAYER, which consists of two layers of phospholipids back to back.

Phospholipid: It is a lipid with a phosphate group attached to them. They have ONE head, TWO tails. The head is known to be polar and hydrophilic (loves water) while the tail is known to be non-polar and hydrophobic (hates water). 

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In the bilayer, the heads are pointing OUTWARD while the tails are hidden in the middle of the bilayer.

Membrane Proteins in the Plasma Membrane: 

Cholesterol: This helps stabilize the phospholipids and keeps them in position.

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Integral Protein: These contain residues with hydrophobic side chains that interact with fatty acyl groups of the membrane phospholipids, thus anchoring the protein to the membrane. They are known to span the entire phospholipid bilayer. Some are anchored to one of the membrane leaflets by covalently bound fatty acids.

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Peripheral Protein: These do NOT interact with the hydrophobic core of the phospholipid bilayer. They are usually bound to the membrane INDIRECTLY by interactions with integral membrane proteins or DIRECTLY by interactions with lipid polar head groups. These localize to the cytosolic face of the plasma membrane (including the cytoskeletal proteins, spectrin and actin) and the enzyme protein kinase C. The enzyme shuttle plays a role in signal transduction.

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Glycolipids: These are components of cellular membranes comprised of a hydrophobic lipid tail and one or more hydrophilic sugar groups linked by a glycosidic bond. Generally, they are found on the outer leaflet of cellular membranes where it plays not only a structural role to maintain membrane stability but also facilitates cell-cell communication

acting as receptors, anchors for proteins and regulators of signal transduction. 

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Both Integral and Peripheral Proteins serve as channels to allow the molecules to enter and leave the cell.

 Review general diffusion. How does it differ from facilitated diffusion? Diffusion: This is the net movement of molecules or atoms from a region of higher concentration to a region of lower concentration (DOWN A GRADIENT). This is driven by a gradient in chemical potential of the diffusing species. What are the three types of diffusion? o Simple Diffusion: This is the movement of molecules across a semipermeable membrane without the help of protein channels. Hydrophobic molecules can freely pass through a cell membrane. Examples are gases such as oxygen, carbon dioxide, and nitrogen. o Facilitated Diffusion: This is the flow of molecules down a concentration gradient, across a membrane, but requires the help of a protein. There are two categories of proteins that assist facilitated diffusion: carrier proteins and channel proteins. This involves proteins, but these proteins do not require the use of ATP.  Carrier proteins are like taxi cabs in a cell membrane. They shuttle molecules from one side of a membrane to the other.  Channel proteins are like tunnels that create a hole across a cell membrane. Channels open to allow molecules to flow through them.

Structure of the cell membrane: phospholipid bilayer, and classes of membrane proteins – receptors, structural proteins, and transporters. Transporters include channels, carriers, and pumps. You should be able to: distinguish among classes of transporters and describe how they permit diffusion (simple and facilitated) across a membrane. You should be able to describe the basic structure of a gated channel and describe the workings of carrier proteins. What is endocytosis, and how is it used to

transport substances through cells? How do pumps allow substances to be transported against concentration gradients? Phospholipid Bilayer: They have ONE head, TWO tails. The head is known to be polar and hydrophilic (loves water) while the tail is known to be non-polar and hydrophobic (hates water). In the bilayer, the heads are pointing OUTWARD while the tails are hidden in the middle of the bilayer. Receptors: There are a variety of different receptors that all have a different structure and function. o Ligand-Gated Ion Channels (Ionotropic Receptors): These are typically the targets of fast neurotransmitters (such as acetylcholine (nicotinic) and GABA). Activation of these receptors results in changes in ion movement across a membrane. They have a heteromeric structure in that each subunit consists of the extracellular ligand-binding domain and a transmembrane domain where the transmembrane domain in turn includes four transmembrane alpha helices. o G-Protein Coupled Receptors (Metabotropic Receptors): This is the largest family of receptors and includes the receptors for several hormones and slow transmitters (such as dopamine, metabotropic glutamate). They are composed of seven transmembrane alpha helices. The loops connecting the alpha helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is usually located in the extracellular domain whereas the binding site for smaller non-peptide ligands is often located between the seven alpha helices and one extracellular loop. o Kinase-Linked and Related Receptors: They are composed of an extracellular domain containing the ligand binding site and an intracellular domain, often with enzymatic-function, linked by a single transmembrane alpha helix. Example: Insulin Receptor. o Nuclear Receptors: These are composed of a C-terminal ligand-binding region, a core DNA-binding domain and a N-terminal domain that contains the AF1(activation function 1) region. The core region has two zinc fingers that are responsible for recognizing the DNA sequences specific to this receptor. The N terminus interacts with other cellular transcription factors in a ligandindependent manner; and, depending on these interactions, it can modify the binding/activity of the receptor.

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Structural Proteins: These are the proteins that are generally fibrous and stringy. They are the most abundant class of proteins in nature. Their main function is to provide mechanical support. Examples: Keratin, Collagen, and Elastin. o Keratins are found in hair, quills, feathers, horns, and beaks. Collagens and Elastin are found in connective tissues such as tendons and ligaments. Collagen is recognized as the most abundant mammalian protein. Structural proteins such as collagen, fibronectin and laminin are utilized in cell culture applications as attachment factors. Transporters: This is a protein that serves the function of moving other materials within an organism. These are vital to the growth and life of all living things. There are several different kinds of transport proteins:

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o Carrier Proteins: These are involved in the movement of ions, small molecules or macromolecules across a biological membrane. These are integral proteins that exist within and span the membrane across which they transport substances. o Channel Proteins: This is a protein that allows the transport of specific substances across a cell membrane. This is a biological macromolecule made up of 20 different amino acids and that the sequence of those chains determines the specific shape and function of the protein. o Vesicular Transport Protein: This is a transmembrane associated protein. It regulates or facilitates the movement by vesicles of the contents of the cell. o ATP-Powered Pumps: These are ATPases that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against a chemical concentration gradient or electric potential. Such pumps maintain the low calcium (Ca2+) and sodium (Na+) ion concentrations inside virtually all animal cells relative to that in the medium and generate the low pH inside animal-cell lysosomes, plant-cell vacuoles, and the lumen of the stomach. Gated Channels: This is an ion channel in a cell membrane that opens or closes in response to a stimulus or to a change in pressure, voltage or light. o Voltage-Gated Channel: Example: Sodium and Potassium Channels of the Nerve Axons and Nerve Terminals. o Extracellular Ligand-Activated Channels: Most are regulated by ligands that are neurotransmitters. o Intracellular Ligand-Gated Ion Channels: These include CFTR and some other ABC family members as well as ion channels involved in sense perception. These are often activated indirectly by GCPRs. Other common intracellular ligands which activate these kinds of channels include calcium ions, ATP, cyclic AMP and GMP as well as phosphadidyl inositol (PI). How do Carrier Proteins work? o The carrier proteins facilitate diffusion of molecules across the cell membrane. The protein is imbedded in the cell membrane and covers the entire membrane. This is important because the carrier must transport the molecule in and out of the cell. What is Endocytosis? How is it used to transport substances through cells? o This is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of plasma membrane, which then buds off inside the cell to form a vesicle containing the ingested material. o This includes Pinocytosis (Cell Drinking) and Phagocytosis (Cell Eating). o ACTIVE TRANSPORT FORM. How do pumps allow substances to be transported against concentration gradients? o These are ATPases that use the energy of ATP hydrolysis to move ions or small molecules across a membrane against a chemical concentration gradient or electric potential

Excitable tissues: 1. Basic definitions: moving ions create a current; resistance to ion flow; conductance; electrical potential difference. Ohm’s Law. You should be able to:

identify ions that typically produce membrane potentials and describe why a cell membrane works as a capacitator. How would capacitance be measured across a membrane? 

Moving Ions Create a Current: When ion channels open, ions may move into or out of the cell. The flow of electrical charge carried by an ion is called the ion’s current. The direction of ion movement depends on the electrochemical gradient of the ion.

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Resistance to Ion Flow: Resistance to current flow comes from two main sources: the resistance of the cell membrane and the internal resistance of the cytoplasm. The phospholipid bilayer of the cell membrane is normally an excellent insulator, and a membrane with no open ion channels has very high resistance and low conductance. If ion channels open, ions (current) flow across the membrane if there is an electrochemical gradient for them. Opening ion channels therefore decreases the membrane resistance.

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Conductance: The ease with which ions flow through a channel is called the channel’s conductance. Channel conductance varies with the gating state of the channel and with the channel protein isoform.

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Electrical Potential Difference: An electrical potential difference exists between two locations when there is a net separation of charge between the two locations. This is termed the membrane potential of the cell. While this phenomenon is present in all cells, it is especially important in nerve and muscles cells, because changes in their membrane potentials are used to code and transmit information.

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Ohm’s Law: Ohm’s law says that current flow (I) is directly proportional to the electrical potential difference (in volts, V) between two points and inversely proportional to the resistance (R) of the system to current flow: I=V×1/RI=V×1/R or I=V/R.I=V/R. In other words, as resistance R increases, current flow I decreases.

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Identify ions that typically produce membrane potentials and describe why a cell membrane works as a capacitator. How would capacitance be measured across a membrane? o Two Factors that influence: The uneven distribution of ions across the cell membrane. Normally, sodium, chloride and calcium are more concentrated in the extracellular fluid than in the cytosol. Potassium is more concentrated in the cytosol than in the extracellular fluid.  Differing membrane permeability to those ions. The resting cell membrane is much more permeable to K+ than to Na+ or Ca+. This makes K+ the major ion contributing to the resting membrane potential. Capacitance refers to the ability of the cell membrane to store charge (like a battery). A system with high capacitance requires more energy for current flow because some of the energy is diverted to “storage” in the system’s capacitor. In the body, the extracellular and 

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intracellular fluids are the conducting materials, and the phospholipid cell membrane is the insulator. o Capacitance is inversely related to distance: As distance between the conducting compartments increases, capacitance decreases. The stacked membrane layers of the myelin sheath increase the distance between the ECF and ICF and therefore decrease capacitance in that region of the axon. Decreasing membrane capacitance makes voltage changes across the membrane faster—part of the reason conduction of action potentials is faster in myelinated axons. 2. Resting membrane potentials, equilibrium potentials, and action potentials: unequal distribution of change between extracellular and intracellular spaces. You should be able to: define equilibrium potential for ions and predict ion movement. How are ions distributed among intracellular, extracellular, and plasma compartments? What is depolarization? Repolarization? Hyperpolarization? You should be able to predict whether ion movement will produce one of these three situations. What kinds of changes in ion conductance may be expected in an action potential? How do ion channels permit these changes? 

Resting Membrane Potential: This is determined by the combined contributions of the (concentration gradient ×× membrane permeability) for each ion. The resting membrane potential of living cells is determined primarily by the K+ concentration gradient and the cell’s resting permeability to K+, Na+, and Cl-. A change in either the K+ concentration gradient or ion permeabilities changes the membrane potential.

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Equilibrium Potential: The equilibrium potential for an ion is the membrane potential at which the electrical and chemical forces acting on the ion are equal and opposite.

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Action Potential: These are very brief, large depolarizations that travel for long distances through a neuron without losing strength. Their function is rapid signaling over long distances, such as from your toe to your brain.

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Equilibrium Potential for Ions: The equilibrium potential for an ion is the membrane potential at which the electrical and chemical forces acting on the ion are equal and opposite.

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Predict Ion Movement: At rest, the cell membrane of a neuron is only slightly permeable to Na+. If the membrane suddenly increases its Na+ permeability, Na+ enters the cell, moving down its electrochemical gradient.The addition of positive Na+ to the intracellular fluid depolarizes the cell membrane and creates an electrical signal. The movement of ions across the membrane can also hyperpolarize a cell. If the cell membrane suddenly becomes more permeable to K+, positive charge is lost from inside the cell, and the cell becomes more negative (hyperpolarizes). A cell may also hyperpolarize if negatively charged ions, such as Cl-, enter the cell from the extracellular fluid.

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How are ions distributed among intracellular, extracellular and plasma compartments?

o Neurons contain a variety of gated ion channels that alternate between open and closed states, depending on the intracellular and extracellular conditions. A slower method for changing membrane permeability is for the cell to insert new channels into the membrane or remove some existing channels. Ion channels are usually named according to the primary ion(s) they allow to pass through them. There are four major types of selective ion channels in the neuron: (1) Na+ channels, (2) K+ channels, (3) Ca2+ channels, and (4) Cl− channels. Other channels are less selective, such as the monovalent cation channels that allow both Na+ and K+ to pass. 

Depolarization: A decrease in the membrane potential difference of a cell.

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Repolarization: Phase during which depolarized membrane returns to its resting potential.

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Hyperpolarization: A membrane potential that is more negative than the resting potential.

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What kinds of changes in ion conductance may be expected in an action potential? How do ion channels permit these changes? o What are the ion channels that are associated with conductance?  Mechanically gated ion channels are found in sensory neurons and open in response to physical forces such as pressure or stretch. 

Chemically gated ion channels in most neurons respond to a variety of ligands, such as extracellular neurotransmitters and neuromodulators or intracellular signal molecules.

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Voltage-gated ion channels respond to changes in the cell’s membrane potential. Voltage-gated Na+ and K+ channels play an important role in the initiation and conduction of electrical signals along the axon.

3. Graded potentials and action potentials: what is the difference between them? You should be able to: distinguish between ion channels controlled by mechanical, electrical, and chemical stimuli. What kinds of channels are active in each kind of stimulus? How are action potentials propagated along an axon? How are potentials measured in excitable tissues? What are temporal and spatial summation, and where can each occur? 

Graded Potentials: They are variable-strength signals that travel over short distances and lose strength as they travel through the cell. They are used for short-distance communication. If a depolarizing graded potential is strong enough when it reaches an integrating region within a neuron, the graded potential initiates an action potential.

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Action Potentials: They are very brief, large depolarizations that travel for long distances through a neuron without losing strength. Their function is rapid signaling over long distances, such as from your toe to your brain.

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Distinguish between ion channels controlled by mechanical, electrical, and chemical stimuli? o In neurons of the CNS and the efferent division, graded potentials occur when chemical signals from other neurons open chemically gated ion channels, allowing ions to enter or leave the neuron. Mechanical stimuli (such as stretch) or chemical stimuli open ion channels in some sensory neurons.

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How are action potentials propagated along an axon? o The action potential generated at the axon hillock propagates as a wave along the axon. The currents flowing inwards at a point on the axon during an action potential spread out along the axon and depolarize the adjacent sections of its membrane. If sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. Once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. At the molecular level, this absolute refractory period corresponds to the time required for the voltage-activ...