Intro to CNS

Question 1

Conductance (g) of K is _______ than conductance of Na

Answer 1

20x greater

Question 2

What is the Nernst potential? Its value for K, Na, Cl?

Answer 2

membrane potential at which the ion is in electrochemical equilibrium across the membrane.

Ek = -75mV, ENa = +55mV, ECl = -69mV

Question 3

What are some generalities of ion channels?

Answer 3

1. Integral membrane proteins
2. Multiple membrane-spanning domains
3. Form a hydrophilic channel in the center (?)
4. Selective for ions and regulated by changes in the cellular environment
5. Multiple gene products; multiple subunits
6. Glycosylated on the extracellular side
7. Consensus sequences for kinases
8. Exhibit specificity for the ion(s) that permeates the channel
9. Ionic movement is driven by its electrochemical gradient

Question 4

2 functional classification of ion channels are?

Answer 4

Passive and Active

Question 5

Passive ion channels are

Answer 5

non-gated, always open

Question 6

Active ion channels are

Answer 6

gated (i.e. closed and open states of the channel are regulated)

Question 7

What are the protein families that allow ionic passage across membrane

Answer 7

ATPase driven pumps, transporters, ion channels

Question 8

What are some types of gating for ion channels?

Answer 8

1. membrane potential difference (i.e. voltage gated)
2. small extracellular molecules (i.e. neurotransmitters)
3. other membrane proteins (e.g. beta-gamma subunits of G proteins
4. Intracellular molecules (e.g. ions, ATP)

Question 9

What are leak channels

Answer 9

Channels that are open at resting membrane potential

can be either active or passive
all passive channels are leak channels

Question 10

Resting membrane potential of neurons

Answer 10

Em (or Vm) = -60mV

Question 11

What causes a resting membrane potential?

Answer 11

1. Intracellular proteins are predominately anions
2. There are leak channels in the plasma membrane that allow K and Cl to move across membrane (Na is too big)
3. Conductance of K is 20x greater than Na
4. This causes unequal distribution of Cl, K, Na across membrane

Question 12

What is the distribution of Cl, K, and Na

Answer 12

K is higher inside the cell, whereas Na and Cl are higher outside

Question 13

What opposes some of the leak (in a resting membrane potential)?

Answer 13

NaK ATPase pump

It moves Na ions out and K ions into cell

Question 14

Why do Action potentials occurs?

Answer 14

Voltage operated sodium channels open in the membrane in response to localized depolarization, which increase Na current

Question 15

Compare voltage gated potassium channels to voltage gated sodium channels

Answer 15

Voltage gated potassium channels also open; however, their opening is more gradual and their inactivation is slower than the voltage gated channels

Question 16

Some facts of action potentials

Answer 16

1. all or none
2. amplitude of ~100mV (thus reaches approx +40mV because resting membrane potential is -60mV)
3. 1-10 msec in duration
4. propagated through cycles of depolarization and repolarization

Question 17

What are synaptic potentials?

Answer 17

Small grade potentials that can lead to they initial depolarization that cause an action potential

Question 18

Synaptic potential facts

Answer 18

1. Local
2. Can summate in time and space
3. Only a few mV in size and a few msec in duration

Question 19

What are the two types of synaptic potentials

Answer 19

1. Excitatory, postsynaptic potential (EPSP)
   - membrane potential becomes more positive, and if it increases enough, threshold leading to AP will be reached
2. Inhibitory postsynaptic potential (IPSP)
   - membrane potential becomes more negative
   - impact is on summating EPSP which will now not reach threshold

Question 20

Two mechanisms by which an EPSP can occur

Answer 20

1. Increased conductance
   - Open ligand gated ion channel for Na or Ca
   
   • Nicotinic cholinergic receptor
   • Glutamate receptor
2. Decreased conductance
   - Close a leak channel for potassium
   
   • Usually due to changes in phosphorylation of channel
   • regulated by 2nd messenger cascades; G protein coupled receptors

Question 21

Mechanism for production of IPSP

Answer 21

• Increased conductance to either potassium or chloride
  
  • Ligand gated Cl channel (e.g. GABA receptor)
  • GPCR activation, resulting in opening of K channels
    
    • By direct interaction b/w channel protein and G protein
    • By changes in phosphorylation state of closed K channels (mediated by 2nd messenger cascades

Question 22

Example of neurotransmitter

Answer 22

Norepinephrine (a prototype catecholamine)

Question 23

Norepinephrine CNS distribution and physiological roles

Answer 23

Noradrenergic neurons (neurons that utilize NE) are located in medulla oblongata, pons, and midbrain

• these regions are called reticular activating system
• important in arousal (wakefulness) and regulation of autonomic functions like breathing and BP

Question 24

Synthesis of norepinephrine

Answer 24

1. tyrosine –> 3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
2. DOPA –> dopamine by decarboxylase
   
   • low substrate specificity
3. dopamine –> NE by dopamine beta hydroxylase
   
   • will oxidize almost any phenyl-ehtylamine to the corresponding phenylethanolamine

Question 25

Primary regulation of NE synthesis is at

Answer 25

tyrosine hydroxylase (TH)

Question 26

Tyrosine hydroxylase essential co-factor

Answer 26

tetrahydrobiopterine BH4