Ion Channels, Part 2

Front 1

What is the nicotinic, cholinergic receptor?

Back 1

A ligand gated cation channel that antiports Na and K

Front 2

What activates the nicotinic, cholinergic receptor?

Back 2

ACh

Front 3

What does nicotinic, cholinergic receptor activation produce?

Back 3

depolarizing post-synaptic potentials.

*aka EPSPs.

Front 4

What receptor is the site of action of nicotine?

Back 4

Nicotinic, cholinergic receptor

Front 5

What happens when ACh is released by a motor neuron and it binds to a nicotinic, cholinergic receptor?

Back 5

The receptor depolarizes skeletal muscle

Front 6

What is myasthenia gravis?

Back 6

The immune system makes Abs to the skeletal muscle nicotinic receptor resulting in muscle weakness.

Front 7

What is the 5-Ht3 ionotropic receptor?

Back 7

A ligand-gated cation channel that is selective for Na and K

Front 8

What is the GABA-A ionotropic receptor?

Back 8

A ligand-gated anionic channel that conducts Cl- current.

Front 9

What does GABA-A activation produce?

Back 9

Cl- selective anion channel that when activated by GABA mediates hyperpolarizing inhibitory postsynaptic potentials (IPSPs).

Front 10

What do benzodiazepines and barbiturates do?

Back 10

Act on the GABA-A receptor to make you sleepy!

Front 11

What is the pentameric glycine ionotropic receptor?

Back 11

A ligand-gated Cl anion channel that is activated by binding of glycine inhibitory IPSPs.

Front 12

What is the function of the pentameric glycine ionotropic receptor?

Back 12

Modulates excitatory neurons that mediate wake state and response to auditory and tactile stimuli.

Front 13

What is startle disease?

Back 13

"hyperplexia". Characterized by an abnormal response to auditory or tactile stimuli.

Front 14

What is the glutamate-activated cation channel?

Back 14

A ligand-gated channel that conducts Na and K that is activated by glutamate.

Front 15

What does activation of the glutamate-activated cation channel produce?

Back 15

EPSP and it is involved in long-term potentiation of memory.

Front 16

What channel is involved in Rasmussens encephalitis?

Back 16

NMDA (glutamate receptor)

Front 17

What is the purinergic ligand-gated cation channel?

Back 17

1. A post-synaptic ATP-activated cation channel that is permeable to Na, K and Calcium
2. involved in excitatory synaptic transmission and regulation of blood clotting.

Front 18

What is the role of ATP in purinergic ligand-gated cation channels?

Back 18

Channels activated by synaptic co-release of ATP in catecholamine (NE) containing synaptic vesicles.

ATP-Ca channels are synergistic w/ alpha1 receptors and enhance NE mediated constriction.

Front 19

What is the cystic-fibrosis transmembrane receptor? (CFTR)

Back 19

A ligand-gated channel that contains two internally homologous domains. It is a Cl- selective channel coupled to cAMP regulation.

*IMPORTANT transport pathway in secretory and absorptive epithelia in lung tissues. There are numerous mutations in this channel, one of which causes cystic fibrosis

Front 20

What is the CIC Cl- channel?

Back 20

Cl- selective voltage-sensitive anion channel in skeletal muscle.

It regulates the regulation of electrical excitability in skeletal muscle. Modulates the threshold potential for activation in skeletal muscle.

ALSO mediates Cl- transport in epithelia

Front 21

What mutation causes becker and thompson myotonia? what marks becker and thompson myotonia?

Back 21

CIC Cl- channel; hyperexcitability of skeletal muscle causing delayed relaxation

Front 22

What is the tetrameric intracellular IP3 activated channel?

Back 22

VERY IMPORTANT CHANNEL IN SMOOTH MUSCLE!!!

1. intracellular cation channel permeable to Na, K and CALCIUM
2. Activated by binding of IP3 and Ca
3. mediates excitation-contraction in smooth muscle and participates in intracellular Calcium release.

Front 23

What is the mechanism of action of the CIC Cl- channel?

Back 23

In smooth muscle ER, IP3 channel activation is coupled to alpha1-b receptor activation by NE, which in turn activates phospholipase C. PLC promotes the release of phospho-inositol bis phosphate (PIP2) w/ final conversion to IP3.

Front 24

What is the function of the tetrameric intracellular IP3 channel?

Back 24

Mediates excitation-contraction coupling in smooth muscle and participates in intracellular Ca release.

Front 25

What is the function of the tetrameric ryanodine receptor (RYR) Ca release channel?

Back 25

aka: CICR

Promotes rapid intracellular Ca release.

Front 26

What is the RYR1 channel activated by? where is it located?

Back 26

Direct mechanical coupling to Cav channels in skeletal muscle.

located in skeletal muscle

Front 27

What activates RYR2 and RYR3 channels? where is it located?

Back 27

Activated by elevation of cytoplasmic Ca due to plasma membrane Ca entry.

Located in heart, smooth muscle and neurons

Front 28

What is dysregulation of the RYR3 receptor linked to? what drug is more selective for the RYR3 channel?

Back 28

malignant hyperthermia.

Dantrolene, an antagonist drug

Front 29

What is the multi-meric ORAI store operated Ca channel?

Back 29

Located on the plasma membrane on non-excitable cells such as epithelial cells and lymphocytes.

*basically it is a plasma membrane Calcium channel. Orai is activated by IP3-activated Ca release and CICR from SER

Front 30

What is STIM?

Back 30

An SER "calcium sensor" and is activated when SER Ca levels are lowered.

Front 31

What is another name for the ORAI channel?

Back 31

I-CRAC for Ca-release activated Ca current or SOC channel for store-operated Ca entry.

Front 32

What is the essential function of a channel?

Back 32

To form a aqueous channel pore so that ions flow across the hydrophobic membrane bilayer down the electrochemical gradient.

Front 33

What is the structure of most eukaryotic channels?

Back 33

Aqueous pores are located at the center of an oligomeric rosette-like arrangement of homologous subunits.

Ea. subunit is a polypeptide that weaves through the membrane several times

Front 34

What are gap junctions?

Back 34

Protein channels that connect two cells w/ a large, unselective pore that allows ions and small molecules as large as 1 kDa to pass through.

Front 35

What is a connexin?

Back 35

A subunit that is an integral membrane protein that, (along w/ 5 other subunits) forms a gap junction.

Each subunit has four identifiable hydrophobic transmembrane segments

Front 36

What effect does intracellular Ca concentration have on the probability a gap junction will be open/closed?

Back 36

*elevated [Ca] increase the probability that the gap junction will be closed.

Front 37

Where are the N1 AChRs located?

Back 37

At the neuromuscular junction

Front 38

Where are the N2 AChRs located?

Back 38

In the ANS on the postsynpatic membrane of the postganglionic sympathetic and parasympathetic neurons and in the CNS

Front 39

what change in the nicotinic receptor occurs during development?

Back 39

In fetal skeletal muscle the subunit composition is alpha2-beta-gamma-delta but in the adult there is a transition from gamma to epsilon, so the adult nicotinic receptor is alpha2-beta-epsilon-delta

Front 40

How many subunits does the nicotinic receptor have?

Back 40

5. The ACh receptor shows pentameric radial symmetry that corresponds to a rosette.

Front 41

How can ALL potassium channels be modulated?

Back 41

By reversible phosphorylation

Front 42

What is the structure of the Kv channel?

Back 42

4 identical tetrameric subunits w/ six transmembrane regions on ea. subunit.

Front 43

What is the structure of small and intermediate conductance calcium activated potassium Channels? (SKca and IKca)

Back 43

They have the same basic structure as the Kv channel, but these channels are voltage independent and only activated by Calcium.

Front 44

What is the voltage sensitive region of the Kv channel?

Back 44

region 4

Front 45

What is the structure of the inward rectifier Potassium channel?

Back 45

Kir is a tetramer w/ two membrane spanning regions.

Front 46

What is the structure of the dimeric tandem two-pore potassium channel (K2P)?

Back 46

Basically a tandem duplication of a Kir channel

Front 47

What is the hyperpolarization-activated, cyclic nucleotide-gated cation channel (HCN)?

Back 47

Plays a CRITICAL role in the automaticity of the heart and rhythmically firing neurons of the brain.

Front 48

What regulates HCN channels?

Back 48

Cyclic nucleotides and they are also voltage sensitive.

Front 49

What are CNG channels?

Back 49

A family of cation-selective channels that are directly activated by intracellular cGMP or cAMP.

These channels play a IMPORTANT role in visual and olfactory sensation.

Front 50

What activates the CNG channel?

Back 50

binding of cAMP or cGMP

Front 51

What are the TRP channels?

Back 51

Sensory channels that transduce sensory information

Front 52

What activates the TRPV channel?

Back 52

Capsaicin, the "hot" ingredient of chili peppers. Appears to function in pain and temperature sensation

Front 53

What activates the TRPM channel?

Back 53

Menthol, the "cool"-tasting substance in eucalyptus leaves.

Front 54

What is the structure of the voltage-gated sodium channels? (Nav)

Back 54

Four domains, each domain containing the S1 to S6 structural motif that is homologous to the Kv K+ channel monomers. Each domain has 1 voltage sensing region.

Front 55

What unique structure are the Nav channels associated with?

Back 55

A unique family of auxiliary beta-subunits, modifying gating behavior and membrane localization of the channel-forming alpha-subunit.

Front 56

What do mutations in the Nav beta-subunit result in?

Back 56

Altered Nav function which causes Long QT (LQT3) syndrome.

*LQT3 occurs at fast cardiac paces (i.e. exercise/stress)

Front 57

What is the structure of voltage-gated Calcium channels?

Back 57

Cav channels are multisubunit complexes (similar to Nav) that are called the alpha-subunit. the alpha subunit has four voltage sensor regions and in addition there are three accessory proteins that are involved in channel regulation. (alpha2-delta and a gamma subunit)

Front 58

What is the general structure of ligand-gated channels? What channels have this basic structure?

Back 58

*basic structure: pentamers w/ 4 transmembrane regions.
*channels that follow this: ACh, 5-HT, GABA, Glycine

Front 59

What major structures are absent on ligand-gated channels?

Back 59

Phosphorylation sights, so they are NOT regulated by reversible phosphorylation

Front 60

What is the structure of the Glutamate channel?

Back 60

ligand channels that have only three membrane spanning regions per monomer

Front 61

What is the structure of the purinergic ligand-gated channels?

Back 61

A pentameric dimer w/ two membrane spanning regions

Front 62

What is the CFTR channel?

Back 62

a Cl- channel that modulates fluid balance in the lung alveoli.

*cystic fibrosis is caused by mutations in the NBD1/NBD2 regions

Front 63

What is the structure of the CIC family of Cl- channels?

Back 63

have FIFTEEN (15!!!) membrane spanning regions on EACH monomer

Front 64

What is the structure of the ORAI channel and STIM?

Back 64

ORAI is a monomer until SER Ca levels decline.

The decline in SER [Ca] activates STIM aggregation.

STIM aggregates causing ORAI aggregation and formation of Ca channels.