BIOL 4004 Exam 1

Refractory period

The time it takes for a sufficient number of voltage-gated Na+ channels to recover from inactivation.

ATP-driven pumps

Transporters which couple uphill transport (against its gradient) to the hydrolysis of ATP.

Voltage-gated channels

Channels that open and close in response to changes in membrane potential.

Passive transport

Term used to refer to movement of a molecule across a membrane down its concentration gradient.

Transporters

General term for proteins that bind specific solutes and undergo conformational changes to move the solute across a membrane.

True

T/F: The salutatory conduction of an action potential only occurs along myelinated axons.

False

T/F: Membrane depolarization will always trigger an action potential.

False

T/F: Aquaporins actively transport water across a membrane against its concentration gradient.

False

T/F: Eukaryotic cells have very high cytosolic concentrations of Ca2+ compared to extracellular levels.

False

T/F: Action potentials are able to 'jump' across the small, extracellular space that separates a presynaptic membrane from a postsynaptic membrane (i.e. the synaptic cleft).

Antiporters

Transporters which move two solutes across the membrane in opposite directions; one solute moves uphill (against gradient) and the other solute moves downhill (with gradient)

Initial segment

Proximal region of an axon displaying a high concentration of voltage-gated Na+ channels; it is the site where action potentials are triggered.

True

T/F: Ion-driven coupled transporters are said to mediate secondary active transport, since the energy of ATP hydrolysis is used to indirectly drive transport of a solute uphill.

True

T/F: The passive transport of charged molecules across a membrane is influenced by both its concentration gradient and the membrane potential; concentration gradient is the only influence on the passive transport of uncharged molecules.

False

T/F: Action potentials travel faster along unmyelinated nerves axons than myelinated nerve axons.

False - nonpolar (hydrophobic) molecules can diffuse, but the passage of polar (hydrophilic) molecules is limited due to the hydrophobic interior of a lipid bilayer

T/F: The hydrophobic cores of lipid bilayers allow diffusion of polar (hydrophilic) molecules, but limit the passage of nonpolar (hydrophobic) molecules

Size & solubility in oil (hydrophobicity) - smaller and more hydrophobic molecules diffuse more rapidly than larger or more hydrophilic

Rate at which a molecule will diffuse across a lipid bilayer depends on _________ & ____________

1. Small nonpolar molecules (O2, N2, steroid hormones)

2. Small uncharged polar molecules (water, urea, glycerol)

3. Large uncharged polar molecules (glucose, sucrose)

4. Charged molecules - even small ions are almost a billion times less permeable than water; allows different solute concentrations to be maintained across the membrane

List the molecules rate of diffusion in order from fastest to slowest:

- Large uncharged polar molecules

- Small nonpolar molecules (e.g. O2 and CO2)

- Small uncharged polar molecules

- Charged molecules (e.g. Na+ and K+)

Na+ & Cl-

The cation found in highest concentration within the extracellular space is ___, and is balanced mainly by high extracellular concentration of ___

K+ & variety of negatively charged organic molecules

The cation found in highest concentration within the cytosol of a cell is ___, and is balanced by ________

1. Drive active transport

2. Convey electrical signals (e.g. nerve cells)

3. Produce ATP (Mitochondria, chloroplasts, bacteria)

Cells can store energy in the form of electrochemical gradients across membranes;

this energy can be used to (3):

Membrane transport proteins - each is specific for a molecule or class of molecule, most are "multipass" transmembrane proteins which form a continuous path for molecules to avoid the hydrophobic core of membranes

The passage of ions and small solutes across a membrane is facilitated by specialized ___________

True

T/F: Transport of solutes across a membrane is a highly controlled process

Channels & Transporters

Two major classes of membrane transport proteins, based on method of transport __________ & ___________

Channels

Form narrow, hydrophilic pores through which the solute passes by passive diffusion; discriminate mainly on basis of charge and size; when open, molecules of the appropriate size and charge can pass through ("Trap door", usually only one type of ion can pass)

Transporters

Also known as "carriers" or "permeases", they bind solute and undergo conformational change to transport across the membrane; only allow passage of molecules which bind to specific sites on the protein; slower than channels; bind molecules on one side of the membrane and change conformation to allow release of the molecule on the other side of the membrane ("Turnstile")

Passive or downhill or "Facilitated diffusion"

Transport that follows a gradient

Active or uphill

Transport that goes against a gradient and requires energy

Passive (downhill transport)

All channels are ________, but only some transporters are _________; require no metabolic energy

Concentration gradient

For uncharged molecules, PASSIVE transport is driven by, and the direction of transport is determined by, its ___________ _________ across the membrane

Electrochemical gradient

For charged molecules (e.g. ions), PASSIVE transport is driven by, and the direction of transport is determined by, its _____________ __________ across the membrane

Membrane potential

The difference in the electrical potential on each side of the membrane; caused by small excesses of positive or negative charge in the neighborhood of the membrane

True

T/F: The inside of most plasma membranes is usually more negative, favoring the uptake of positive ions, opposing the entry of negatively charged ions, and opposing the efflux of positively charged ions

False - They may work in the same direction (ion gets pulled in same direction) or against each other (ion gets pulled in opposite directions)

T/F: The membrane potential and concentration gradient can only influence transport in the same direction

Glucose Transporter; transporter switches randomly between two conformations, exposing binding sites for glucose on either the interior or exterior of a cell; transport occurs in BOTH directions (direction depends on glucose concentration gradient)

An example of a transporter which carries out PASSIVE transport of an uncharged molecule; found in the plasma membrane of liver cells (hepatocytes)

Into the cell - extracellular concentrations will be higher so transport will flow in with its gradient

After a meal, which direction will transport of glucose take place?

Out of the cell - the hormone Glucagon will influence the breakdown of glycogen into glucose within the cell, so high concentrations of glucose in the cell causes it to flow out of the cell with its gradient

When blood sugar is low, what direction will glucose transport occur?

Active (uphill)

Most transporters, but no channels, carry out __________ transport; essential to maintain intracellular concentrations; must be coupled to some sort of metabolic energy; the carrying of solutes against their electrochemical gradient

Pumps

Another name for transporters that carry out active transport

False - transporters cannot ever be simultaneously open on both sides of the membrane; they have three conformations: open to one side of the membrane, an intermediate state where it is not open to either side, and open to the opposite side of the membrane

T/F: A transporter can be simultaneously open to both sides of the membrane

Maximum rate of transport (Vmax)

Occurs when all binding sites on a transporter are occupied, or the transporter is 'saturated'; it is the rate at which the transporter can flip between its two conformational states

Affinity of a transporter for its solute (Km)

The concentration of a solute when the rate of transport is 1/2 Vmax

Competitive inhibitors & noncompetitive inhibitors

Similar to enzymes, binding of substrates to transporters can be blocked by what two things?

Competitive transporter inhibitors

Molecules which bind to the same site as solutes

Noncompetitive transporter inhibitors

Molecules which bind to sites other than the binding site but negatively affect the structure of the transporter

Passive transport or facilitated diffusion

Type of transport that is driven by the electrochemical gradient; occurs downhill or along the solutes electrochemical gradient; rate of transport depends on the transporter's Vmax and Km

Active transport

Type of transport that requires energy input; occurs uphill or against the solutes electrochemical gradient or concentration gradient

1. Coupled transporters - the uphill transport of one solute is driven by the coupling of downhill transport of a second solute

2. ATP-driven pumps - the uphill transport of one solute is coupled to the hydrolysis of ATP (P-type, F-type, V-type, ABC transporters)

3. Light-driven pumps - found in bacteria and archaea; uphill transport of a solute is coupled to energy produced by light

The three ways of driving active transport (describe)

Uniporters - mediate the passing of a single solute type across a membrane (PASSIVE transport)

Coupled transporters - transport of one solute depends on the transport of a second solute (ACTIVE transport); the energy released as one solute (typically an inorganic ion) moves down its gradient is used to drive transport of a second solute uphill or against its gradient; two types of coupled transporters:

1. Symporters (co-transporters) - transport two solutes in the same directions

2. Antiporters (exchangers) - transport two solutes in opposite directions

Types of transporters (describe)

Active transport is carried out by energy stored in electrochemical gradients; the rate of transport depends on the size of the electrochemical gradient of the first solute - the larger the gradient (more energy), the faster the transport; in plasma membrane Na+, and in membrane organelles H+, flowing down their gradient provides free energy to transport molecules against their gradients

What provides energy to drive Coupled transporters?

ATP-driven Na+-K+ pumps

Continuously pump Na+ out of the cell (against its gradient) to maintain the Na+ gradient; indirectly drives coupled transport; mediate primary active transport

Secondary active transport

The energy of ATP hydrolysis is used to indirectly drive transport of a solute uphill (e.g. ion-driven coupled transporters)

Primary active transport

The free energy of ATP hydrolysis is used to directly drive the transport of a solute against its concentration gradient (e.g. ATP-driven coupled transporters)

False - binding of glucose and Na+ is COOPERATIVE; the binding of one causes a conformational change that increases the transporter's affinity to bind the other

T/F: Binding of glucose and Na+ in transporters of intestinal epithelial cells is independent

False - they are symporters; the concentration of Na+ is much, much higher in the extracellular side, so glucose and Na+ both bind on the extracellular side and are released on the inside of the cell

T/F: Glucose transporters in intestinal epithelial cells are antiporters

Usually contain 10 or more transmembrane alpha-helices; the two halves of the transporter are inverted to each other; binding sites are located midway through the membrane; can work in the opposite direction if both the ion (travelling downhill) and solute (travelling uphill) concentrations are reversed

Structure of transporters

Na+-H+ exchanger

Decreasing pH results in increasing activity; uses Na+ gradient for energy; couples influx of Na+ to an efflux of H+ (removes H+ from the cytosol to maintain optimum pH for cytosolic enzymes to function)

Na+-driven Cl--HCO3- exchanger

Couples influx of Na+ and HCO3- to an efflux of Cl- and H+ (e.g. influx of NaHCO3 and efflux of HCl); more efficient than Na+-H+ exchanger; for each Na+, one H+ is removed from the cytosol and another is neutralized

Na+-independent Cl--HCO3- exchanger

Lowers cytosolic pH; activity increases as cytosol pH increases; moves HCO3- out of the cell down its gradient; facilitates the movement of CO2 out of red blood cells (in the form of HCO3-) as the cells move through lung capillaries

In intestinal epithelial cells, Na+-driven glucose symporters (Na+-glucose transporters) are found only on the apical membrane of the cells (adjacent to the lumen of the gut); active transport of the Na+-driven glucose symporters raises intracellular glucose concentrations; glucose uniporters are found only on the basal-lateral membrane and transport glucose out of the cell into the extracellular fluid via PASSIVE transport

Describe how asymmetric distribution of transporters drives unidirectional nutrient uptake

1. P-type pumps

2. ABC transporters

3. F-type ATPases (ATP synthases)

4. V-type pumps

What are the four classes of ATP-driven pumps (transport ATPases)?

P-type pumps

Transporter (pump) that transports ions; responsible for setting up and maintaining ion gradients across the membrane (Na+, K+, Ca2+, H+); composed of multipass transmembrane proteins; become phosphorylated during the pumping cycle

ABC transporters

Transporters which couple the transport of small molecules to ATP hydrolysis

V-type pumps

Transports H+ into organelles such as lysosomes or synaptic vesicles; constructed from multiple subunits

F-type ATPases

Work in reverse compared to other pumps; use H+ gradient to synthesize ATP from ADP and inorganic phosphate; found in bacteria, the inner membrane of mitochondria, and the thylakoid membrane of chloroplasts

An action potential arrives at the muscle cells, depolarizing the cell membrane and opening voltage-gated Ca2+ channels. Then, Ca2+ flows down its electrochemical gradient into the cytosol. Increased cytosolic Ca2+ levels triggers Ca2+-gated Ca2+ channels in the Sarcoplasmic Reticulum, causing more Ca2+ to flow into the cytosol resulting in muscle contraction. For muscle relaxation, the Ca2+ must be pumped back into the Sarcoplasmic reticulum to lower cytosolic Ca2+ levels.

Explain Ca2+ regulation of cardiac muscle contraction.

Low & High

Eukaryotic cells have very _____ concentrations of Ca2+ in their cytosol compared to very _____ concentrations of Ca2+ in the extracellular space

Contain 10 transmembrane alpha-helices which are connected to three (3) cytosolic domain: Activator domain, phosphorylation domain, and nucleotide-binding domain. It also contains two Ca2+ binding sites between the transmembrane domains

The Sarcoplasmic reticulum contains P-type Ca2+ ATPases, explain them.

1. In the ATP bound, unphosphorylated state, the transporter is open to the cytosolic side and has two Ca2+ binding sites available

2. Ca2+ binds, triggering the passageway to close

3. ATP is hydrolyzed and an aspartate is phosphorylated in the phosphorylation domain

4. ADP is replaced by an ATP and the Ca2+ binding sites open to the lumen of the Sarcoplasmic reticulum

5. Two Ca2+ leave the transporter and are replaced by two H+

6. The passageway closes to the Sarcoplasmic reticulum lumen

7. The phosphorylated aspartate loses its phosphate group and the pump returns to it's initial, unphosphorylated state

Explain how P-type Ca2+ ATPase returns Ca2+ to the Sarcoplasmic reticulum.

Maintain important Na+ and K+ gradients in organisms (higher K+ in the cell, higher Na+ outside the cell); Na+ gradient is used to drive many cellular processes; is an ANTIPORTER - moves 3 Na+ out of the cell and 2 K+ into the cell, both are transported against their gradients and receive the energy to do so through ATP hydrolysis

Explain the functions of the Na+-K+ (ATPase) pumps.

1. Three (3) intracellular Na+ ions bind to the pump

2. ATP is hydrolyzed, phosphorylating the pump which changes its conformation, releasing the Na+ ions on the other side of the membrane

3. Two (2) extracellular K+ ions bind to the pump, triggering the pump to release its' phosphate group

4. The release of the phosphate group triggers a conformational change, releasing the K+ ions on the other side of the membrane

Explain how the Na+-K+ pump works.

They contain two highly conserved ATP-binding domains on the cytosolic side:

1. ATP binds to each domain, causing a conformational change which releases the bound solute to the extracellular side of the membrane

2. The two (2) ATP hydrolyze, causing the pump to return to its initial state with the solute binding site available

Explain the mechanism of how ABC transporters work.

Multidrug resistance (MDR) protein

A type of ABC transporter present in many types of human cancer cells; makes cells resistant to many different drugs used in cancer therapy

Membrane channels

Transmembrane, aqueous pores that allow the passive movement of solutes into or out of the cell; do not go through conformations each time a solute passes, however they can be open or closed.

Large nonspecific:

1. Gap junctions - allow communication between cells

2. Porins - found in the outer membrane of mitochondria

Small specific:

1. Aquaporins - Facilitate passage of water through the membrane

2. Ion channels - transport inorganic ions

Two types of large, nonspecific channels found in organisms.

Two types of channels in the plasma membrane that are narrow, specific, and can open or close.

Aquaporins

Allow for the rapid movement of water across the plasma membrane (in single-file fashion); commonly found in kidney epithelial cells and exocrine cells (secretory cells); one side of the pore is lined with carbonyl oxygens while the other is lined with hydrophobic amino acids; impermeable to inorganic ions, H+, etc.

Rapidly open and close; transport is passive and solute move down/along their electrochemical gradients; Ion channels are SELECTIVE - only allow certain ions to pass which is determined by the narrowest part of the channel, the SELECTIVITY FILTER, which determines rate of passage, selectivity is based on AMINO ACID DISTRIBUTION lining the channel as well as DIAMETER AND SHAPE of the ion channel (a change in a single amino acid residue within a channel can change its specificity); they are gated, allowing the channels to open and close rapidly

Properties of Ion channels.

Voltage-gated channels

Channels which respond to changes in the voltage across a membrane

Ligand-gated channels:

1. Transmitter-gated channels - binding of an extracellular neurotransmitter

2. Ion-gated channels - binding of an intracellular mediator such as an anion

3. Nucleotide-gated channels - binding of an intracellular nucleotide

Channels that are controlled by the binding of a molecule to the channel; three (3) types

Mechanically-gated channels

Channels that are controlled by mechanical stress applied to the channel

Acetylcholine

Neurotransmitter released by axons at neuromuscular junctions

Acetylcholinesterase

Enzyme which degrades the neurotransmitter acetylcholine

Action potential (nerve impulse)

Self-propagating wave of depolarization along the plasma membrane

Adaptation

A decrease in the response of a neuron in the case of unchanging, prolonged stimulation

Axon

Nerve cell projection which conveys electrical signals away from the nerve cell body to target organs or neurons

Cooperative binding

When the binding of one solute causes a conformational change that increases the binding affinity of a second solute

Coupled transporters

Transporters which couple the uphill transport of one solute to the downhill transport of a second solute

Dendrites

Nerve cell projections which function in the reception of signals

Electrically excitable cells

Cells capable of generating action potentials (e.g. neurons or muscle cells)

Excitatory neurons

Neurons which release neurotransmitters that have a positive effect on a target and encourage the formation of action potentials

Excitatory postsynaptic potential (excitatory PSPs)

A small depolarization in the postsynaptic membrane of an excitatory synapse

Inhibitory neurons

Neurons which release neurotransmitters that have a negative effect on a target and discourage the formation of action potentials

Inhibitory postsynaptic potential (inhibitory PSPs)

A small hyperpolarization in the postsynaptic membrane of an inhibitory synapse

Ion channels

Hydrophilic pores in the membrane which allow the passive transport of specific inorganic ions

Ion-gated channels

Channels that open in response to the binding of an ion

K+ leak channels

Channels that are open in unstimulated, resting cells and make the plasma membrane more permeable to K+ ions

Membrane depolarization

A change in membrane potential which decreases or reverses the voltage difference across the membrane

Motor neurons

Cell that, in response to sensory input, carry information from the central nervous system to the target organs and tissue

Multiple sclerosis

A type of autoimmune disease resulting in the destruction of myelin in the central nervous system

Myelin sheath

Electrically insulating membrane of Schwann cells (in peripheral nervous system) or Oligodendrocytes (in central nervous system) wrapped around nerve axons