Driving forces

Electrical driving force

movement of charged particles along an electrical gradient is due to electrostatic attraction (between opp charges) or repulsion (same charges) 

Resting membrane potential

Voltage difference across the plasma membrane in millivolts when the cell is at rest (-70mV is the standard)

step 1 create resting membrane potential

Cell establishes and maintains concentration gradients for Na+, K+, and large molecules (dna and proteins)

step 2 create resting membrane potential

Na and K ions diffuse through the membrane down their concentration gradients (leak channels)

step 3 create resting membrane potential

Diffusion through the membrane causes charge separation, creating a membrane potential. Difference exerts electrical gradient = independent driving force of ionic movement

Step 4 create resting membrane potential

Movement of charges continues and permeability determines the resting membrane potential 

Proteins central to establishing and maintaining concentration gradient

Na/K ATPase pump

Concentration gradient

• NA K ATPase establishes and maintains unequal concentration of NA and K ions 

• Pumps 3 Na out and 2 K in (net +1 per cycle)

Na in cell menbrane

low intracellular concentration

K in cell membrane

high intracelllular concentration

equilibrium potential of K

-90mV

Increasing K concentration

cell membrane potential increases (more +)

Resting potential

-70mv, large amount of K move out the cell membrane

small net diffusion of Na inside the cell to neutralize potential created by K

Neurons

dendrites, axon, axon terminal,

Graded potentials

Local changes in membrane potential that decay over short distances

• Brief injection of current typically the result of synaptic transmission and opening of ligand gated channels 

• Decay over short times 

• Upward deflection = decrease in potential

• Downward = increase in potential 

Temporal summation

• neuron receives rapid information from one other synapse

Spatial summation

neuron receives inputs from multiple other neurons

Action potential

• brief all or nothing reversal in membrane potential, lasting 1 millisecond, brought about by rapid change in membrane permeability to NA and K ions 

  • Relies on voltage gated Na channels for rising and voltage gated K for falling

Threshold potential

-50mV (amount needed to get action potential) 

• Once crossed, depolarization occurs by positive feedback loop

Na gated channels

opens quickly in response to depolarization allowing Na+ to flow down its electrochemical gradient into the cell. Responsible for rising phase

K gated channels

opens more slowly in response to depolarization allowing K ions to flow out of the cell down their electrochemical gradient 

Voltage gated channels deactivated

1. Na: closed but capable of opening at threshold (fast) 

2. K: closed but capable of opening at threshold (slow)

Activated voltage gated channels

1. Na: open

2. K: open, will close again below threshold (slow) 

Inactivated voltage gated channels

1. Na: closed and not capable of opening. Inactivation can only be removed by repolarization to 70mV

Refractory periods

periods where spikes cannot generate after action potential

Absolute refractory periods

brief period during a second spike cannot be generated. It begins with the activation of voltage gates NA channels and ends when their inactivation is removed 

Relative refractory

brief period following a spike which is higher intensity stimulus is needed to generate a second spike. It begins when Na channel inactivation is removed and ends when the voltage gated K channels deactivate

Synapses

junction between two neurons or between a neuron and muscle or gland that enables one cell to electrically and/or biochemically influence another cell 

Two types: electrical and chemical

Chemical synapses

 neurotransmitters released from the presynaptic terminal via Ca mediated exocytosis 

• Bind to receptors on post synaptic membrane, typically ligand gated ion channels that open and produce PSP. This is a graded potential

Electrical synapse

The charges flowing into the presynaptic terminal are directly relayed to the postsynaptic neuron because the ions themselves flow through gap junctions 

• Faster

• Physically have to connect to allow charges to flow through gap junction channels 

Inhibitory postsynaptic potential (IPSP)

Hyperpolarizing events that bring Vm away from threshold from firing an action potential (GABA and Glycerine) 

• Cl and K flux in IPSP 

Excitatory postsynaptic potential (EPSP) 

Depolarizing event that brings Vm closer to threshold for firing an action potential (Glutamate and acetylcholine) 

• Na and Ca flux

Fast synapses and ligand gated ion channels

Respond within ms to a neurotransmitter

• Exoplasmic domain of ligand gated channel processed a neurotransmitter binding site

  • Binding causing immediate conformational change 

Slow synapses and GPCR’S

Functions of nervous system operate within seconds or minutes

Duration of neurotransmitter action is limited by

• Diffusion out the synaptic cleft (results in dilution) 

• Degradation of extracellular enzymes

• Reuptake into the presynaptic terminal by transporter proteins or glial cells 

Cost of effective escape

• Energy spent

• Time cost: not doing what you were doing

• Opportunity: lost chances to feed, etc

• This can be controlled by the animal

Benefits of effective escape

• You make your own luck

• Probability of surviving this encounter

• This can be controlled by the animal 

How does the animal control cost and benefits

intensity and threshold

Intensity of escape

1. Low intensity: less likely to succeed, lower cost to execute

2. High intensity: very likely to succeed, higher cost to execute 

Threshold of escape behavior

1. Low threshold: very likely to succeed, high cost from false alarms 

2. High threshold: less likely to succeed, lower cost from false alarms 

Ultimate hypothesis of escape

Its about the why of an adaptation: in what way does it help the animal

Proximate hypothesis of escape

Pick a model system 

Steps in generating escape reflex

• Sense the stimulus

• Integrate sensory information

• Reach threshold for reflex

• Trigger contraction in muscles

Proximate questions for escape

• What cells are involved? 

• How do they work to make the reflex happen

  • Requires the nervous system

Sufficiency

•  is the part good enough to get an escape response 

  • Ex: electrically activating lg neuron gets identical reflex

Necessary

Does inhibiting the part allow the signal to go through or does it not produce the same response

Protein sorting

proteins can go on 10 different paths

Cytoplasm

not a special protein

Nucleus

• To enter: Needs nuclear localization signal produced by the protein to enter

• To exit: NES nuclear export signal needed

Mitochondria

• Needs matrix targeting sequence

  • Has to be at N terminal of protein to stay unfolded 

Chloroplasts

• Needs stroma targeting sequence

  • Has to be at N terminal to stay unfolded 

Peroxisome

• Has enzymes that break down fatty acid chains to then sent for the mito to use 

• Needs to peroxisomal targeting sequence 

  • Must be at c terminus

ER

• Er signal peptide needed

  • Must be at N terminal 

  • Attaches to the ribosome binded to mRNA molecule 

    • SRP bind to the ER peptide signal 

  • goes through translocon

SRP

•  halts translocation; gets bound by SRP receptor in rough ER membrane 

  • Disconnects 

Translocon

will transport protein into ER by having the ribosome sit on top of it and allow the ER signal peptide translate the protein into the ER

co-translational translocation

Protein goes into the ER

Post translational translocation

• fully translates first 

  • mitochondria/chloroplast: translate, translocate, fold

  • nucleus/peroxisome: translate, fold, translocate 

ER→ golgi

no additional sequences needed

Golgi→ plasma membrane

• Clathrin (coat protein) present to do endocytosis 

Golgi → ER

• KDEL sequence is needed to enter 

  • 4 amino acids in this order 

  • Has to be at the C terminal 

• KDEL and KDEL receptor dont bind at higher pH’s

  • Do bind at lower pH 

• Coat protein 1

Golgi→ lysosome

• Mannose- 6- phosphate needed "lysosomal targeting signal” 

  • Added in the ER 

• Cis golgi: adds p sugar

• Trans golgi: removes last sugar before moving it into an endosome that merges with the lysosome (vesicle helps transport it) 

  • pH lowers throughout the process 

• Coat proteins: broad membrane that forms vesicle

  • Choose which proteins will be taken up 

  • Mediate transport of proteins from trans golgi to lysosome 

• Coat protein 2 is present

Chaperone proteins

• are needed to keep proteins unfolded