Ion Channels and Transporters Flashcards
two general types of transport proteins
carrier and channel proteins
channel proteins
discrimination based on size and charge
open channels and allow ions and water to slip through
movement is fast and direction is dependent on the solute concentration gradient
carrier proteins
enzyme-like binding site for solute molecule
transmembrane transport involves conformational change
movemen of ions is slow and reversible
two types of channels
ion-specific channels for ion permeability, found in most if not all cell types, used for inter-and intracellular signaling
non-specific channels - allow many kinds of molecules to pass through
gap junction
comprised of six subunits in a hexagonal array and allows passage of water soluble molecules between cells
degree of opening of the junction is controlled by the concentration of intracellular ions
alpha toxin
water soluble protein from staphylococcus aureus
forms a pore in the membrane of many cell types and allows passage of water-soluble, uncharged molecuels less than 2 kDa, ATP, and Ca2+
two general types of carriers
transporters (or exchangers) - proteins that selectively ransport large water-soluble molecules and ions across membranes down their concentration gradient, facilitated diffusion
ATPases - transporters that couple transport with hydrolysis of ATP, energy expenditure allows movement up concentration gradient
glucose transporters
a family of transporters that bind glucose on the EC surface and leads to release on the cytoplasmic side
driven by high EC glucose concentrations
glucose-Na transporter
in some cells such as kidney tubules and intestinal cells, glucose concentration is too high, and this transporter binds NA+ and glucose simultaneously
transport is facilitaed by coupling it to the movemen of Na+ down its concentration gradient
basic amino acid transporter
a Na+ independent transport of basic and neutral amino acids into cells
neutotrasnmitter transporter
reseponsible for the reuptake of neurotransmitters at nerve terminals
Na-H exchanger
couples the movement of Na+ into cells twith H+ out
since metabolic activity generates H ions, this exchanger helps regulate intracellular pH
Na/K-ATPase
moves Na+ out and K+ into cells, responsible for creating Na+ and K+ concentration differences across the membrane
maintains cellular membrane potential and cell volume
uses about 25% of total energy consuption in humans at rest
Ca-ATPase
transports Ca2+ out of cells or into organelles
maintains low intracellular Ca2+ level which is important in cell signalling
H-ATPase
moves H+ out of the cell or into organelles
inmitochondria, this protein works in revers and generates ATP
ABC transproters
a family of proteins with both transporter and ATPase activity
are used to move a wide variety of molecules into cells and organelles faster than would occur by simple diffusion
How many subunits are ion-specific channels made up of?
six transmembrane domains
How many subunits form the central pore region of a ion-specific channel?
four - allows ions to mvoe in and out of the cell
How fast is the transition form an open to closed state in an ion-specific channel?
instantaneous
mechanisms that affect ion-specific channel opening and closing
changes in membrane potential
binding of a ligand to the channel
mechanical stretching of the membrane
two substates of close ion-specific channels
closed but activateable
close and inactivated
two ways of reactivating inactivated ion-specific channels
changing of membrane potential or unbinding of ligand
factors that affect the magnitude of the current through an open ion-specific channel
driving force (Vm - Eion) for the conducting ion and the duration that the channel stays open
current through an open channel obeys Oh’s Law (Iion = dV/Rm)
probability that an ion-specific channel will open at a specified voltage or ligand concentration
follows a Poisson distribution (bell-shaped curve)
types of ion-specific channels
ligand-dependent (or ligand-activated) channels
voltage-dependent (orvoltage-activated) channels
stress-activated channels
ligand-dependent (or ligand-activated) channels
opened when a ligand binds to the channel
ex. neurotransmitter-activated, Ca-activated K channels, ATP-activated, cGMP-dependent
voltage dependent (or voltage-activated) channels
channels are opened when the membrane potential is changed (either depolarized or hyperpolarized
ion-specific channels opened by depolarization
Na-specific channels, Ca-specific channels
ubiquitous
ion-specific channels opened by hyperpolarization
K-specific channels
ubiquitous
stress-activated channels
opened when membrane is mechanically stretched
found in auditory receptors and cutaneous pressure receptors
voltage-gated Na+ channels
composed of three subunits, alpha subunits has the critical functional properties
alpha subunit has 300-400 amino acid repeats
each repeat contains six predicted transmembrane domains
each repeat also contains a pore-loop (P-loop) whose residues line the pore
S4 transmembrane domains of residues function as sensors that move out during membrane coupled to channel opening
the intracellular domain has an inactivating mechanism that occludes ion conduction shortly after the channel opens
ATPases
protines which couple transport with hydrolysis of ATP
energy expenditure enables movement of solutes up their concentration gradient
Ouabain and digoxin
commonly used Na/K ATPase inhibitors used as glycosides
digoxin is commonly used as a cardiac glycoside to treat congestive heart failure
Describe the mechanism of the SERCA Ca2+ pump
distinct E1 and E2 states
two key structures of the SERCA pump
E1 Ca bound state and E2-P Ca unbound state
in the E2 state, the N and P domains have closed around the phosphorylaspartate analog and caused the calcium-binding site to be disrupted
common functional domains of ion channels
selectivity pore, ion filter channel, gate
domains of the serca pump
nucleotide binding domain (N)
actuator domain (A)
phosphorylation domain (P)
stimuli that activate gated ion channels
voltage, extracellular ligand, intracellular ligand, mechanical forces
describe the membrane topology of the voltage-gated ion channel
What creates the selectivity filter?
created by loops between the fifth and sixth helix
two broad categories of mammalian K+ channels
structure of the bacterial two TM K+ channel
ions flow are selected by charge, selectivity filter lined by carbonyl oxygens
binding sites are very close together so the potassium ions electrostatically force each other through, creating a high flow rate
