Intro to CNS Flashcards
Conductance (g) of K is _______ than conductance of Na
20x greater
What is the Nernst potential? Its value for K, Na, Cl?
membrane potential at which the ion is in electrochemical equilibrium across the membrane.
Ek = -75mV, ENa = +55mV, ECl = -69mV
What are some generalities of ion channels?
- Integral membrane proteins
- Multiple membrane-spanning domains
- Form a hydrophilic channel in the center (?)
- Selective for ions and regulated by changes in the cellular environment
- Multiple gene products; multiple subunits
- Glycosylated on the extracellular side
- Consensus sequences for kinases
- Exhibit specificity for the ion(s) that permeates the channel
- Ionic movement is driven by its electrochemical gradient
2 functional classification of ion channels are?
Passive and Active
Passive ion channels are
non-gated, always open
Active ion channels are
gated (i.e. closed and open states of the channel are regulated)
What are the protein families that allow ionic passage across membrane
ATPase driven pumps, transporters, ion channels
What are some types of gating for ion channels?
- membrane potential difference (i.e. voltage gated)
- small extracellular molecules (i.e. neurotransmitters)
- other membrane proteins (e.g. beta-gamma subunits of G proteins
- Intracellular molecules (e.g. ions, ATP)
What are leak channels
Channels that are open at resting membrane potential
can be either active or passive
all passive channels are leak channels
Resting membrane potential of neurons
Em (or Vm) = -60mV
What causes a resting membrane potential?
- Intracellular proteins are predominately anions
- There are leak channels in the plasma membrane that allow K and Cl to move across membrane (Na is too big)
- Conductance of K is 20x greater than Na
- This causes unequal distribution of Cl, K, Na across membrane
What is the distribution of Cl, K, and Na
K is higher inside the cell, whereas Na and Cl are higher outside
What opposes some of the leak (in a resting membrane potential)?
NaK ATPase pump
It moves Na ions out and K ions into cell
Why do Action potentials occurs?
Voltage operated sodium channels open in the membrane in response to localized depolarization, which increase Na current
Compare voltage gated potassium channels to voltage gated sodium channels
Voltage gated potassium channels also open; however, their opening is more gradual and their inactivation is slower than the voltage gated channels
Some facts of action potentials
- all or none
- amplitude of ~100mV (thus reaches approx +40mV because resting membrane potential is -60mV)
- 1-10 msec in duration
- propagated through cycles of depolarization and repolarization
What are synaptic potentials?
Small grade potentials that can lead to they initial depolarization that cause an action potential
Synaptic potential facts
- Local
- Can summate in time and space
- Only a few mV in size and a few msec in duration
What are the two types of synaptic potentials
- Excitatory, postsynaptic potential (EPSP)
- membrane potential becomes more positive, and if it increases enough, threshold leading to AP will be reached - Inhibitory postsynaptic potential (IPSP)
- membrane potential becomes more negative
- impact is on summating EPSP which will now not reach threshold
Two mechanisms by which an EPSP can occur
- Increased conductance
- Open ligand gated ion channel for Na or Ca- Nicotinic cholinergic receptor
- Glutamate receptor
- 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
Mechanism for production of IPSP
- 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
Example of neurotransmitter
Norepinephrine (a prototype catecholamine)
Norepinephrine CNS distribution and physiological roles
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
Synthesis of norepinephrine
- tyrosine –> 3,4-dihydroxyphenylalanine (DOPA) by tyrosine hydroxylase
- DOPA –> dopamine by decarboxylase
- low substrate specificity
- dopamine –> NE by dopamine beta hydroxylase
- will oxidize almost any phenyl-ehtylamine to the corresponding phenylethanolamine
Primary regulation of NE synthesis is at
tyrosine hydroxylase (TH)
Tyrosine hydroxylase essential co-factor
tetrahydrobiopterine BH4
