BIPN 140 midterm 2

Hyperkalemia

Too much K+ in extracellular

causes depolarization

Bring membrane potential close to threshold

Why does hyperkalemia not always cause increase spiking

Inactivation of Na channels at higher voltage

At high but sub-threshold voltage Na channels are more likely to be open and be in a state of inactivation. Cannot close until voltage drops so stuck in inactivation state.

Hypokalemia

Too little K+ extracellularly

causes hyperpolarization

Bring membrane potential away from threshold and make spiking less likely

How could hypokalemia sometimes causes more spiking

At lower voltage Na channels do not inactive

Causing depolarization

After-hyperpolarization rebound

Injecting a hyperpolarizing current for a while then stop injecting it. An action potential will fire shortly after even when the membrane potential is nowhere near threshold.

Na channels inactivation at rest and at hyperpolarize voltage

At rest many are inactivated

Hyperpolarized voltage few are inactivated (can not recover from inactivation)

Channels that carry inward current

Na channels

Calcium channels

Non-selective cation

Calcium channels characteristics

Inactivate slowly → sustained depolarization

“second messenger” can activate other pathways in the cell

Channels that carry outward current

K+ channels

Cl-channels

Pacemaker potential

Neurons that fire by itself without any stimulation

What cause pacemaker potential

Depolarization at hyperpolarized voltage: voltage-independent I_Na or non selective cation current

Transient (short time) hyperpolarization at depolarized voltage: inactivating voltage-dependent I_Ka

Individual AP: inactivaing Na+ current and delay rectifier K+ channels

What causes bursting neuron

Slow depolarization: slow I_Na or I_Ca

Slow hyperpolarization: Slow voltage gated I_k

Electrical Synapses

Connected by gap junctions made of connexins

Gap junctions open and close and are selective by size.

Cells tend to fire together

Faster than chemical synapses and reliable

Chemical synapses

Do not touch separated by a synaptic cleft (20nm)

Amplify signal

Keep cytoplasm of pre- and post- synaptic cells separate

Turn (+) charged signal into (-) signal

Limited by diffusion and reuptake of neurotransmitters

Steps of chemical synapses

1. Depolarization open voltage-gated Ca channels, Ca enter presynaptic terminal

2. Ca trigger exocytosis or vesicles containing neurotransmitters

3. Vesicles are endocytosed and recycled

4. Neurotransmitter diffuse across synaptic cleft and bind to receptors on postsynaptic membrane to open channels and cause signaling

How to know if it is voltage-gated calcium channels

Use Ca-sensitive dyes

Look at reversal potential near E_Ca (I=0 on IV graph)

Measure presynaptic current and block it with Ca channel blockers

How does a decrease in Ca in the extra cellular fluid change the electrical signal (EEP)?

It decrease the amplitude because with less Ca entry fewer NT are released so there is less reposne in the muscle.

Neurotransmitters (NT)

Present in the presynaptic neuron

Released in response to the presynaptic depolarization

Affect the postsynaptic cell by binding to specific receptors

Vesicles

Store neurotransmitters

Same size

Small-molecular neurotransmitter

Small clear-core vesicles

Make in terminal

Recycled by terminal

Close to the presynaptic membrane (readily-releasable pool)

Neuropeptide Transmitter

Large dense-core vesicles

Make in soma

Degraded after release

Further away from the reserve pool

Co-transmitters

when a neuron release more than one neurotransmitters

Amunt of vesicles released depend on the Ca influx

Low frequency stimulation release which vesicles

Clear-core vesicles from the readily-releasable pool

Localized increase in Ca concentration near membrane

High frequency stimulation release which vesicles

Dense-core vesicles and clear-core vesicles in reserve pool

More diffuse increase in the Ca concentration

How vesicles fuse to the axon membrane

SNARE proteins pull vesicles close to the plasma membrane

Synaptotagmin binds to Ca and interact with SNARE to allow the vesicle to fuse

Clathrin

Attach to vesicular membrane and coat the budding vesicle

Binds into a ball-like shape

Help with Endocytosis

Kiss-and-run (flicker-fusion)

Vesicles can release their neurotransmitters without fully fusing with the membrane

Happen with high Ca sustained activity

PSPs

Postsynaptic potential in a neuron

EPP

end plate potential in a muscle

EPPs and PSP

Voltage change caused by neurotransmitter binding in the postsynaptic cell

Tells functions of the postsynaptic cell

Amount of transmitter the presynaptic neuron is releasing

Without stimulation Ca channel flicker open and what is released

mPSP and MEPP

Reducing NT loading into vesicles

Lower amplitude in mPSP and PSP amplitude

No change in mPSP frequency (Ca entry driven)

Amount of neurotransmitter in vesicle

mPSP amplitude: yes

mPSP frequency: no

PSP amplitude: yes

Calcium entry

mPSP amplitude: no

mPSP frequency: yes

PSP amplitude: yes

Ability to release vesicles

mPSP amplitude: no

mPSP frequency: yes

PSP amplitude: yes

Ability of receptors in postsynaptic cell to receive signals

mPSP amplitude: yes

mPSP frequency: no

PSP amplitude: yes

Ionotropic receptors (ligand-gated ion channels)

Directly linked to an ion channel

Fast

• Channel opening/ion movement is fast

• Effects starts after 1-2ms of binding, end 10s of ms later

Metabotropic receptors

Affect neurons by activating G-proteins

Slow

• Effects start after G protein dissociates, diffuses and activates target

• Effects can last minutes

Structure of memtabotropic receptors

G protein-coupled receptors (GPCRs)

G proteins are activated inside the cell

GPCRs

ligand that binds to the receptor that activate a G protein

PSC

Postsynaptic current- the current of a postsynaptic cell

EPSP

PSP that are excitatory if increase the likelihood of firing

Evoke current- something that stimulated presynaptic cells

IPSP

PSP that are inhibitory if decrease the likelihood of firing

Evoke current- something that stimulate presynaptic cells

Differences between EPSP and AP

EPSP

• In dendrite or soma

• Graded potential (big or small depend on amount of NT and number of open channels)

AP

• In axon

• All or nothing each AP is the same frequency can change (except for relative refractory period)

mIPSCs and mEPSCs

Spontaneous current

result of one quantum of NT release from random Ca2+ channel opening

EPSP and IPSP firing

When the sum of EPSP and IPSP reaches threshold

sum spatially (over space) or temporally (over time)

Spatial summation of PSP

Sum of PSP to determine overall membrane potential

Temporal Summation of PSP

Receiving 2 PSP one after anther and the are sum because it last longer than action potential

Ending neurotransmitter signaling

1. Diffusion away from the synapse

2. Reuptake into the presynaptic terminal

3. Enzymatic degradtion

Nicotinic Receptors (nAChRs)

Ionotropic

Present at the neuromuscular junction

Muscarinic Receptors (mAChRs)

Metabotropic

Present in the central nervous system

How to identify the ions that carry the nAChR current

1) use and compare reversal potential

2) Alter ion concentration extracellularly

Glutamate

Use in excitatory neurons in the CNS

AMPARs

Permeable to Na and K

gated by glutamate

Sometime permeable to CA depend on particular subunits

NMDAR

Always permeable to Ca (Need glycine to open)

Blocked by Mg (Mg is kicked out by depolarization)

AVP

NMDAR-selective blocker