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71 Cards in this Set
- Front
- Back
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In voltage-gated K+, Na+, Ca2+ channels, S4 segments have 4 to 7 of what residues?
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Arginine or Lysine
(Positively Charged residues) |
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What segment has the major role in being the Voltage-Sensing Mechanism?
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S4 Segment
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In Sodium and Calcium channels, domains I to IV of the α subunit are homologous to a ? of a voltage gated K+ channel.
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single α subunit
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What is a voltage-gated Ca2+ channel made up of?
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pseudo-oligomerica α1 subunit (transmembrane)
extracellular α2 subunit cytoplasmic β subunit δ and γ membrane spanning subunits |
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What is a voltage-gate K+ channel made up of?
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Four α-subunits
fourcytoplasmic β-subunit |
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What is the extracellular linker region between the S5 and S6 segments called?
What occurs here? |
P (pore) Region
-Ionic Selectivity for permeable cations -Toxins and external blocking molecules |
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What does S6 transmembrane segment form?
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Internal aspect of the ion conduction pathway
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Largest and most diverse family of voltage-gated ion channels
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K+ channels
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What is the primary role of K+ channels in excitable cells?
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Inhibitory effect
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The action of excitatory Na+ and Ca2+ channels are opposed by?
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K+ channels
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What stabilizes the resting membrane potential?
Facilitate repolarization? Shaping of action potentials? |
K+ channels
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What are the five K+ channel classifications?
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Kv Channels (voltage-gated)
Small conductance KCa Channels (Ca2+ activated K+ channel, SKCa and IKCa channels) Large conductance KCa Channels (Ca2+ activated K+ channels, including BKCa and Na+ activated K+ channels) Kir channels (inward rectifier K+ channels) K2P channels (two pore K+ channels) |
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What are the two K+ channel types fall into two main structural families?
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Six Transmembrane Domains
Two Transmembrane Domains |
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What K+ channel has only Two Transmembrane Domains
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Kir Channel
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One subunit of K+ channel contains how many transmembrane segments?
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6 transmembrane segment
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In regards to K+ channels....
The pore-loop structure is located on what segment? (found on top of the the pore) Is responsible for what? |
S5-S6
K+ selectivity |
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How does the K+ channel filter work?
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Distance between oxygen atoms in the ion filter is the same as in water for the K+ ions.
This is what prevents Na+ from entering the channel |
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What are the two conformational states?
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open and closed states
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What are the two modes of inactivation for K+ channels?
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Fast inactivation
Slow inactivation |
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What does the fast voltage-DEPENDENT inactivation in K+ channels?
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N-Terminus of the protein
(N-Type Inactivation) |
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In K+ channels, what does the slow inactivation?
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C-Terminus of the protein
(C-Type Inactivation) |
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Can a beta subunit induce inactivation in K+ channels?
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Yes
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List the general structure of a Kv channel family.
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S1-S6 core
S4 voltage-sensor Inactivation gate |
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In K+ channels, when does the S4 segment move outward across the membrane?
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To open the channel
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What is the N-Type Inactivation in Kv channels also known as?
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Ball-and-chain mechanism
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If a K+ channel does not have an inactivation ball domain, what takes its place to inactivate the α-subunits?
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β-subunits
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What channels are crucial for proper function of the auditory system?
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K+ channels
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What provides a stabilizing mechanism to counteract repetitive excitation and intracellular Ca2+ loading?
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KCa Channels
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What mediates the after hyperpolarizing phase of action potentials in cell bodies of various neurons
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KCa channels
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What triggers the opening of KCa channels?
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[Ca2+]i
(intracellular) |
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Kir channels possesses how many transmembrane domains?
what are they? |
TM1
TM2 |
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In the K+ channels, S5-S6 from pore loops. What does Kir use?
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TM1-TM2
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True or False
Kir channels have a voltage dependent segment |
FALSE
they lack a S4 region |
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K(ATP) channels are inhibited by? Activated by?
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ATP ----> Inhibits
ADP ----> Activates |
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In what cells would you most likely find K(ATP) channels?
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Pancreatic β-Cells
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If inhibition of K(ATP) occurs, what would most likely happen next?
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1). small depolarization
2). activates voltage-gated Ca2+ channels 3). Insulin secretion |
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A low ATP/ADP ratio would mean that K(ATP) channels would be...?
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activated
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K(ATP) channels can be targeted by what group of synthetic drugs?
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Sulfonylureas
(inhibit pancreatic K(ATP) channels and stimulate insulin release) |
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If a person has problems with smooth muscles not relaxing, what channel opener would a doctor most likely prescribe?
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K(ATP) channel
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How to K+ channel openers work?
Name some examples of these drugs |
Closing voltage-gated Ca2+ channels and decreasing intracellular Ca2+
Pinacidil Cromakalim |
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How many Ca2+ ions must bind simultaneously in order to conduct a current?
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2 Ca2+ ions
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Pore loops of each domain have what residue with its negative carboxyl projecting into the pore?
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Glutamate
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What creates the two levels of strong negativity in the external pore that attracts the Ca2+?
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glutamate residues
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Do the Ca2+ ions line up single file or do they go in together?
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line up single file
one is superficial and the other deep |
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Which of the voltage-dependent Ca2+ channels has the most functional properties?
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α1
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α1 subunit is structurally similar to Na+ channels in what ways?
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Four domains
each domain has 6 transmembrane segments S4 has positively charged residue that acts as VOLTAGE SENSOR S5-S6 forms a pore loop |
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What is a major function of voltage-gated Ca2_ channels?
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contribute to the depolarizing phase of action potentials
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What ion is an important second messenger in regulating the activity of a multitude of intracellular proteins and enzymes?
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Ca2+
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What is the process by which an electrical depolarization at the cell membrane leads to cell contraction, such as the contraction of a skeletal muscle fiber?
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Excitation-Contraction (EC) Coupling
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What ion is needed in Excitation-Contraction (EC) Coupling?
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Ca2+
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Name the 5 types of Ca2+ channel characteristics.
What are the basis of these classifications? |
L - type channel
T - type channel P/Q - type channel R - type channel Kinetic Properties Inhibitor Sensitivity |
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What are the two types of L-Type Ca2+ channel inactivation?
which is slow and which is fast? |
Ca2+ dependent inactivation (FAST)
voltage-dependent inactivation (SLOW) |
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Explain how Ca2+ dependent inactivation works
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Increase in [Ca2+]
activates FAST inactivation Ca2+ binding CALMODULIN draws the elbow of carboxyl tail peptide into the Ca2+ channel lumen (blocking it) |
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Explain how Voltage-Dependent inactivation works.
(Ca2+ channels) |
Not enough Ca2+ to bind to every CALMODULIN
some Ca2+ channels escape fast inactivation and SLOWLY inactivate during repolarization the peptide links domains I and II and passes into the vacant intracellular lumen of each of these activated Ca2+ channels. |
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If a patient exhibits signs of cardiovascular disorder, such as angina pectoris and hypertension, what would the doctor most likely provide?
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Ca2+ Channel Blockers
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Where do DHP (dihydropyridines) attach to?
What is their effect? |
S5 - S6 in Domain III
S6 in Domain IV can act as inhibitors or activators |
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This syndrome has characteristics of impairment of presynaptic Ca2+ channels at motor nerve terminals.
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Lambert-Eaton Syndrome
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This syndrome is caused by a point mutation in the CACNA1S gene affecting S4 of Domain II causing defective EC coupling of skeletal muscles.
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HYPOkalemic periodic paralysis
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What channel is important for setting cell resting membrane potential and maintaining proper cell volume?
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Cl- Channels
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True or False
Cl- channels can conduct other anions besides Cl-. |
True
HCO3- I- SCN- NO3- |
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Cl- channel subunits contain how many transmembrane segments?
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1 to 12 transmembrane segments
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List the 4 major types of Cl- Channels
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Voltage-Gated Cl- Channels (CLC)
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ca2+ -activated Cl- Channels (CLCA-n) Ligand-gated anion channels (GABA-A and glycine receptors) |
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What is the most likely effect of benzodiazapen on neurons?
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hyperpolarization
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What does STRYCHNINE do?
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antagonist of glycine receptors (chloride channel)
eliminates GLYCINE-mediated inhibition of the spinal cord and the brain stem leads to seizures, muscle contractions, spasm, respiratory paralysis |
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What do sedative/hypnotic agents such as benzodiazepines (diazepam) and barbiturates (pentobarbital) act on?
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GABA-A receptors in the CNS
causes Chloride entry |
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Class of muscle disorders that are characterized by a delay in the ability to relax from a voluntary muscular contraction.
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Myotonia
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What causes Myotonia?
What types of muscles are affected? |
CLC-1 Cl- channel is unable to repolarize the membrane.
>>>giving rise to repeated action potentials skeletal muscles |
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Loss of which type of Cl- channel leads to myotonia?
Mutation of this gene causes myotonia. |
Voltage-Gated Cl- Channels (CLC)
CLCN1 |
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Myotonia causes muscle --?
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stiffness ;; resulting from continued firing of action potentials in the muscle
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Mutation of ? gene causes Cystic Fibrosis.
What does that gene code for? |
CFTR gene in mamamalian epithelial cells
cAMP-regulated Cl- Channel |
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Describe the structure of a CFTR?
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FIVE DOMAINS
2 membrane spanning domains -form the chlorid ion channel 2 nucleotide binding domains -bind and hydrolyze ATP Regulatory domain |
