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81 Cards in this Set
- Front
- Back
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Why are biological membranes essentially impermeable to ions?
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Because the internal region of the bilayer is very hydrophobic and ions are hydrated w/ water!
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So how do ions cross the membrane then?
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By proteins that are in the membrane.
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What are 3 protein families that have evolved to let ions cross the membrane?
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-ATPase driven pumps
-Transporters -Ion channels |
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What kind of proteins are ion channels?
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Integral membrane proteins
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How are integral membrane ion channels composed?
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From multiple membrane-spanning domains
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What makes up the center of ion channels?
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A hydrophilic channel through which hydrated ions can pass!
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How is the selectivity of ion channels regulated?
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By changes in the cellular environment
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How are ion channels encoded?
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By multiple genes that encode for the multiple subunits.
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What is the extracellular side nature of integral membrane-spanning ion channels?
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Glycosylated
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What is on the INtracellular side of ion channels?
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Consensus sequences for kinases at which the channels will be phosphorylated
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Are ion channels random or specific?
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Specific!
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What is ionic movement through ion channels driven by?
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Electrochemical gradients
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What are the 3 functional classes of ion channels, based on their gating mechanisms?
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-Passive
-Active -Leak |
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What is the gating mechanism of a passive ion channel?
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NON-gated - always open!
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What is the gating mechanism of Active channels?
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Gated - the open/closed states of the channel are regulated.
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What are 5 examples of gating mechanisms of active ion channels?
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-Voltage gating
-Neurotransmitters -Other membrane proteins (B-y subunits of G-proteins) -Intracellular molecules (ATP) -Mechanical signals - pressure or stretch |
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What makes Leak channels unique?
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They are open at resting membrane potential.
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What channels are always leak channels?
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Passive
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Are all leak channels passive?
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No, they can be either passive or active.
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What is a resting membrane potential?
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A potential difference across the membrane of excitable cells.
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What is the resting Em for neurons?
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-60 mV
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What are 3 factors that contribute to the Em being -60?
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1. Intracellular anions are predominantly proteins
2. Leak channels in membrane that allow K and Cl movement 3. 20X higher gK than gNa |
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What do the leak channels in neuron membranes allow for?
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K and Cl movement across the membrane.
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What is the result of there being much higher K conductance across resting neuron membranes than Na conductance??
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Unequal distribuation of K, Cl, and Na across the membrane:
K = inside the cell NaCl = outside the cell |
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What does unequal transmembrane distribution of K/Na/Cl result in?
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Electrical and chemical gradients for the ions
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What is a Nernst potential and what is its neuron value for
-K -Cl -Na |
Em where ion is in transmembrane electrochemical equilibrium
K = -75 mV Cl = -69 mV Na = +55 mV |
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What opposes some of the K leak?
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NaK ATPase
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What causes AP's in the neuron?
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Opening of voltage gated Na channels in response to localized depolarization
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What does the increased sodium currant caused by Na channels opening result in?
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Change in the membrane potential
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What else is opened by membrane depolarization in addition to Na channels opening?
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Voltage gated K channels
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How does the opening and inactivation of K channels compare to those of Na channels?
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-Opening is more gradual
-Inactivation is slower |
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What is the amplitude of AP's?
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~100 mV
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What is the duration of APs?
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1-10 msec
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How are AP's propagated?
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Through cycles of depolarization and repolarization
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What are synaptic potentials?
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Small, graded potentials that can lead to the initial depolarization that causes an AP.
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What are the 2 main features of synaptic potentials to know?
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-Local (mediated by NT's)
-Can summate both in time/space |
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What is the amplitude and duration of synaptic potentials?
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Amplitude = a few mV only
Duration = a few msec only |
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What are 2 types of synaptic potentials?
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-EPSPs (excitatory postsynaptic)
-IPSPs (inhibitory postsynaptic) |
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What change occurs in the membrane potential with an:
-EPSP -IPSP |
EPSP - it becomes more positive
IPSP - it becomes more negative |
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What happens if an EPSP is strong enough?
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The membrane might reach threshold and an AP is generated
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What do IPSPs do?
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Impact on EPSPs so they can't reach threshold
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What are 2 mechanisms by which an EPSP can occur?
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-Increased conductance of Na or Ca
-Decreased conductance of K |
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How are Na or Ca channels that generate EPSPs opened?
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By ligand binding (ligand gated)
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What are 2 ligand gated ion channels that can generate EPSPs when stimulated?
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-Nicotinic cholinergic receptors
-Glutamate receptors |
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What causes decreased K conductance leading to EPSPs?
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Closing of K leak channels, usually due to phosphorylation changes on the channel.
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How are changes in the phosphorylation state of K leak channels regulated?
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Byy GPCR's that use Gs to stimulate PKA to phosphorylate the channels, thus closing them.
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What are 2 mechanisms by which IPSPs can be produced?
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1. Increased conductance of K or Cl
2. GPCR activated opening of K channels |
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What is a Ligand gated chloride channel which can increase Cl conductance to generate an IPSP?
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GABA receptor
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So in general, opening K channels will lead to ____, where closing K channels will lead to ______:
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Open K channel = IPSP
Close K channel = EPSP |
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And what are 2 ways to change the state of a K channel?
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-Direct interactions w/ Gprotein
-Phosphorylation state changes |
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What are 3 types of signaling molecules in the brain?
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-Neurotransmitters
-Neuromodulators -Hormones |
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Where do NT's act, and what is their nature of onset/offset of their effects?
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-Synaptic
-Fast onset, fast offset of effects. |
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Where do Neuromodulators act, and what is the nature of their effect's onset/offset?
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-Nonsynaptic
-Slower |
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What are 3 criteria for the establishment of a molecule as a neurotransmitter?
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-Mechanism for synth/degradation
-Neurons release after an AP -Exogenous chemical mimics |
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What is Co-transmission?
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When multiple signalling molecules are released from a single neuron
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What does Co-transmission usually consist of?
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1. Amine NT released at synapse
2. Peptide released at extrasynaptic sites |
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What are 2 categories of NT's based on their synthesis?
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-Amines
-Neuropeptides |
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Where is each synthesized:
-Amines -Neuropeptides |
Amines = at synapse
NPeptides = in Ribosomes |
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For which type of molecule is synthesis related to release?
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Amines
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What are 4 regulatory mechanisms of amine synthesis?
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-Precursor concentration
-Enzymatic step -End product inhibition -Presynaptic autoreceptors |
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What are the precursors for Neuropeptide synthesis? How is it regulated?
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Precursors = Large proteins
Regulated by Induction |
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Where are NT's stored?
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In synaptic vesicles
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How are synaptic vesicles released?
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By secretory pathways
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What secretory pathway is for:
-Amines -Peptides |
Amines = constitutive secretory pathway
Peptides = regulated secretory pathway |
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What are the 2 distinguishing features of the constitutive secretory pathway?
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-Vesicles are re-used
-Vesicles have proteins needed for release at the active zone |
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What 2 features make the regulated secretory pathway different from constitutive?
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-Vesicles are NOT re-used
-Vesicles fuse with the membrane anywhere, not just at the active zone. |
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Why are mechanisms of NT inactivation very important?
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Because signaling can continue until the NT is removed!
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What are the 4 major mechanisms of NT inactivation?
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1. Reuptake
2. Enzymatic breakdown 3. Astroglia uptake 4. Diffusion |
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What are 3 NT's that demonstrate reuptake inactivation?
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-norepi
-serotonin -dopamine |
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What is a NT that is inactivated by Astroglia uptake?
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Glutamate
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What is the prototypic NT that is inactivated by enzyme?
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Acetylcholine
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What NT's undergo diffusion for their inactivation?
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Peptides
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What is ALWAYS required for NT release?
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Calcium! Increased intracellular calcium.
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What is the normal
-Intracellular calcium conc -Extracellular calcium conc |
Intra = 100 NANOmolar
Extra = 2 MILLImolar |
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So in what direction will Calcium flow if channels are opened?
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INTO the cell
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What are 2 mechanisms for increasing intracellular calcium?
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-Opening ion channels
-Release from intracellular storage sites |
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How does Calcium cause NT release?
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By inducing the fusion of vesicle and plasma membrane to release intravesicular contents.
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What is really responsible for the release of intracellular Ca stores at presynaptic terminals?
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Extracellular calcium regulates the intracytoplasmic release when voltage-gated Ca channels allow it to influx.
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What is the most important source of calcium for NT release?
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Extracellular via influx at voltage-gated Ca channels
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What are the 2 ways by which Ca is then extruded back out of the neuron to prevent neurotoxicity?
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-Ca pumps (use ATP) at the cell membrane and ER membrane
-Ca exchanger (Na/Ca) |
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What is Synaptic Plasticity?
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Changes in synaptic efficiency
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