PNB 2774 block 2

coulombs law

opposite charges attract; like charges apart

insulator

membranes typically prevent charge passage

conductor

membranes CAN allow charge passage

active/passive behaviors

membrane electrical behavior - whether active (channels opening and closing, pumps working) or passive (membrane behaving like components of a circuit) - is responsible for signaling in neurons, muscle, and other cell types!

membrane potential (Vm)

the potential inside the cell (typically negative) relative to the reference potential outside the cell (always assumed to be zero)

contributors to membrane potential: unequal ion distribution and unequal ion permeability

nernst equilibirium

the electrical potential (Vm) at which the diffusional flow of an ion one way is balanced by electrostatic attraction in the other.

equilibrium potential

the membrane potential at which a given ion type’s net flux is zero

nernst potential

describes the membrane potential that a single ion would produce if the membrane were permeable to only that ion.

reversal potential

the membrane potential at which the flux of a given ion type reverses from inward to outward.

depolarization

changing membrane potential to be MORE positive (more +)

hyperpolarization

changing membrane potential to be MORE negative (more -)

repolarization

returning membrane potential at which the flux of a given ion type reverses from inward to outward.

goldman-hadgkin-katz equation

predicts membrane potential that results from the contribution of all ions that are membrane-permeant

neurons

nerve cells that are capable of initiating and conducting electrical activity throughout the body

neuroglia

cells that support the neurons

dendrites

receive incoming signals; passive graded synaptic potentials

cell body

integrates multiple incoming signals via summation

axon

carries the output signal: an all or none action potential.

sub-threshold

no action potential unless they summate over threshold to yield an AP

action potentials

an all or none wave of elevated potential that will result in some action on the part of the cell. these actions may include: vesicle release, muscle contraction, signal propagation.

steps of an action potential

1. resting membrane potential: leak channels active; voltage-gated channels closed (de-activated)

2. depolarizing stimulus (synapse, gap junction, electrode..)

3. membrane depolarizes to threshold. voltage-gated Na+ channels open quickly and Na+ enters cell, starting to depolarize cell. Voltage-gated K+ channels are opening.

4. rapid Na+ entry fully and quickly depolarizes cell.

5. V-gated Na+ channels slowly becoming blocked, while delayed V-gated K+ channels are opening.

6. K+ leaves cell through open K+ channels (V and Leak); membrane potential repolarizes.

7. V-gated Na+ channels close fast; remain blocked. V-gated K+ channels stay open, K+ leaves cell: an ‘after’ hyperpolarization (AHP) results

8. V-gated K+ channels slowly close, less K+ efflux. V-gated Na+ channels slowly unblock, stay closed.

9. Cell returns to rest: ion permeability channel states, and membrane potential (Vm) at initial REST states.

action potential: sodium channels

• Na+ channels have two gates: activation (open/close) and inactivation (block/unblock)

• Na+ channels open: sodium flows IN, cell depolarizes.

• with POSITIVE voltage:

  • Na+ channels activate fast

  • Na+ channels inactivate slowly.

• at resting membrane potential, the activation gate closes the channel.

• depolarizing stimulus arrives at the channel. activation gates open.

• with activation gate open, Na+ enters the cell.

• inactivation gate closes and Na+ entry stops.

• During repolarization caused by K+ leaving the cell, the two gates reset to their original positions.

• with NEGATIVE voltage:

  • Na+ channels de-activate fast, and un-inactivate slow.

action potentials: potassium channels

• K+ channels have ONE gate: activation ONLY.

• K+ channels open: potassium flows OUT, cell repolarizes

• with POSITIVE voltage:

  • K+ channels activate slowly

  • K+ channels DON’T inactivate.

• with activate gate open, Na+ enters the cell. K+ channels not yet activated; little K+ efflux.

• during repolarization caused by K+ leaving the cell, the two gates reset to their original positions. K+ channels VERY activated; much K+ efflux

• with NEGATIVE voltage:

  • K+ channels de-activate slowly

action potential: refractory period

the neuron needs the after-hyperpolarization (AHP) phase to: unblock Na+ channels, close K+ channels, reset ionic gradients return to rest.

Action potentials: initiation

axon hillock and initial segment: a ‘trigger’ segment for AP initiation. high density of voltage-gated sodium channels that trigger action potentials. ultimate output of dendritic integration.

action potential: myelination

myelin sheath: 10-160 concentric wrappings of glial membrane around axon. myelin alters distribution of Na+ and K+ channels, and result in saltatory conduction. myelination can increase the speed of conduction by a factor of 100. myelination is done by glial cell types:

• oligodendrocytes: in CNS

• schwann cells: in PNS

synapse

a point of connection between two neurons

• the basic structural mechanism of communication between neurons or to effector cells (muscle, heart, glands)

electrical synapses

• bi-directional signaling. direct electrical couples. second cell mirrors first one.

• gap junctions! connexons, hemi-channels.

chemical synapses

• anterograde (forward direction) signaling: pre to post synapse.

• presynaptic vesicles hold neurotransmitters (NT)

• post synaptic receptors!

• vesicles —> fusing and releasing NTs

synaptic transmission: PRE-synaptic steps

1. an action potential depolarizes the axon terminal.

2. depolarization opens voltage-gated Ca2+ channels and Ca2+ enters the cell.

3. calcium entry triggers exocytosis of synaptic vesicle contents. the neuronal sensor for Ca2+ is called synaptotogmin.

4. NT diffuses across synaptic cleft; binds to receptors on post synaptic cell,

5. NT binding initiates a response in the postsynaptic cell.

vesicle exocytosis cycle entails…

1. filling (with NT; using transporters and pumps)

2. vesicle translocation (using cytoskeleton and motor proteins)

3. docking (using SNARe proteins)

4. priming (using SNARes)

5. fusion with membrane

vesicle endocytosis entails..

1. vesicle membrane translocation

2. coating with clathrin (usually)

3. fission of coated vesicle from membrane. A protein called dynamin helps with this pinching off.

4. uncoating from clathrin.

5. recycling (by several paths)

SNARes: priming / fusing molecules

v-SNAREs: vesicular SNARes. many kinds but KEY one is synaptotogmin (Ca2+ sensor)

t-SNAREs: Target SNARes (terminal membrane)

Botulinum toxin: cleaves SNAREs

ligand-gated ion channel

• fast synaptic transmission (<100 ms)

• opens ion channels (typically)

• receptor and channel part of the same protein.

• little amplification (1 or 2 NT opens one channel)

• IONOTROPIC receptor.

G-protein coupled transmission

• slow synaptic transmission (>100 ms)

• opens OR closes ion channels, among other things.

• receptor and channels (if used) are separate proteins

• amplification (I N T may affect many channels)

• METABOTROPIC receptor; 2nd messengers

post-synaptic graded potentials: summation for integratoin

spatial summation: two (or more) roughly-instantaneous PSPs from different locations sum up across space.

• summation of several subthreshold signals result in an action potential

  • three excitatory neurons fire. their graded potentials are all below threshold

  • graded potentials arrive at trigger zone together and sum to create a suprathreshold signal.

  • an action potential is generated

• postsynaptic inhibition; an inhibitory presynaptic neuron prevents an AP from firing

  • one inhibitory and two excitatory neurons fire

  • the summed potentials are below threshold, so no AP is generated.

temporal summation

two (or more) non-simultaneous PSPs from the same location (usually) sum up over time.

• no summation: two subthreshold graded potentials will not initiate an action potential if they are far apart in time.

• summation causing action potential: if two subthreshold potentials arrive at the trigger zone within a short period of time, they may sum and initiate an action potential

termination of action

• diffusion away from synapse

• re-uptake by pumps and transporters

• cleavage by enzymes

glutamate

main location: CNS

excites neuronal firing

major excitatory NT

GABA

main location: CNS

inhibits neuronal firing

major inhibitory NT

glycine

main location: CNS (scattered)

inhibition in many cases

acetylcholine (ACh)

main locations: nerve-muscle connections; autonomic synapses; some CNS synapse

functions: stimulates muscle contraction; slows heart rate; rest and digest

norepinephrine

locations: autonomic synapses; some CNS syanpases

functions: speeds heart rate; fight or flight; emotion or arousal

serotonin

locations: pons, medulla, etc

functions: broad effects

dopamine

locations: basal ganglia; frontal cortex; limbic (emotional) system

functions: plays a role in motivation and reward.

characteristics of muscle tissue

1. excitability: outside stimuli can initiate electrical changes in the muscle fiber (cell), leading to contraction of that muscle fiber.

2. contractility: stimulation of muscle fiber can lead to contraction or shortening of the muscle fiber.

3. elasticity: a muscle fiber’s ability to return to its original length when the tension of the contraction is released.

4. extensibility: the ability of a muscle fiber to be stretched beyond its relaxed length.

muscle tissue types

1. skeletal muscle: moves skeleton around joints; there are over 700 skeletal muscles.

2. cardiac muscle: heart pumping

3. smooth muscle: involuntary; digestive system (peristalsis), blood vessels (constriction), etc.

skeletal muscle is composed of:

• connective tissue

• muscle fascicles (composed of individual muscle fibers)

• blood vessels

• nerves

motor units

• a motor unit consists of a single motor neuron and the muscle fibers it controls.

• a motor unit controls only a few muscle fibers in an entire muscle. a muscle may have many motor units.

• larger muscles have more units than do smaller muscles.

• each muscle fiber obeys the all-or-none principle. a muscle fiber contracts completely or not at all: when a motor unit is stimulated, all of muscle fibers under its control will contract.

henneman’s size principle

as force increases in a muscle, more and larger motor units are recruited to generate larger force.

whole-muscle properties

• not all muscle cells in a muscle contract at the same time (only the ones activated by the same neuron.

• the number and types of motor units that are activated determines the strength of the contraction:

  • small units and/or smaller number of units at low freq. = weak contraction.

  • large units and/or larger number of units at greater freq. = stronger contraction.

• muscle tone: the continued steady, low level of contraction that stabilizes joints and maintains general muscle health.

neuromuscular junction

neuron/axon

1. synaptic knob: expanded end of the neuron

2. synaptic vesicles: membrane-bound sacs filled with acetylcholine (ACh)

3. synaptic cleft: narrow space separating the synaptic knob from motor end plate.

4. motor end plate: region of sarcolemma (muscle cell plasma membrane) across the synaptic knob that has folds and indentations to increase the surface area in that region

5. ACh receptors: ionotropic receptors in the motor end plate that bind to ACh

6. acetylcholinesterase (AChE): an enzyme in the synaptic cleft that rapidly breaks down ACh

muscle fiber

structural terminology: typical cell vs. muscle cell

plasma membrane = sarcolemma

cytoplasm = sarcoplasm

smooth ER = sarcoplasmic reticulum

muscle-cell specific structure:

• transverse tubules (T-tubules) — deep invaginations of sarcolemma; extend into sarcoplasm.

• terminal cisternae: Ca2+-filled saccs at end of sarcoplasmic reticulum.

excitation-contraction coupling

1. somatic motor neuron releases ACh at neuromuscular junction

2. net entry of Na+ through ACh receptor-channel initiates a muscle action potential.

3. action potential in t-tubule alters conformation of DHP receptor

   • DHP = dihyopyridine L-type calcium channel

4. DHP receptor open RyR Ca2+ release channels in sarcoplasmic reticulum and Ca2+ opens enters cytoplasm.

   • RyR = ryanodine receptor calcium channel

5. Ca2+ binds to tropanin, allowing actin-myosin binding

6. myosin heads execute power stroke

7. action filament slides toward center of sacromere.