Lec. 6: Action Potentials

Contrast the sorts of volume changes that take place in a cell that is in an iso-osmotic solution of particles that freely cross the membrane (penetrating solutes) with that of an iso-osmotic solution of particles that cannot cross the plasma membrane (non-penetrating solutes). In other words, explain how an iso-osmotic solution is not necessarily an isotonic solution

*Iso-OSMOTIC* is the term used for two solutions whose OSMOLARITIES are equal... *Iso-TONIC* however is or refers to a solution with the same SOLUTE concentration. In a solution, some compounds dissociate, so even though the osmolarities may be consistent, the tonicities may not be if the solute dissociates and therefore has only half the concentration of its osmolarity.

Define threshold, and relative and absolute refractory period. Explain the state of ion channels and the stimulus amplitude required to generate an action potential during each.

*Threshold*: membrane potential required to cause an action potential. If point not reached, nothing will happen. *Absolute refractory period*: no stimulus can trigger another action potential (Na close and K channels open). It represents the time required for Na to return to its resting position or reset itself. *Relative refractory period*: only larger than normal stimulus can initiate new action potential (Na reset and K still open)

Describe the property of a solution that "osmolarity" quantifies.

Quantifies the # of solute particles in a solution

Explain how water moves across plasma membranes

Water moves across plasma membranes through aquaporins, which are almost always open. So even though water cannot diffuse across the membrane, they easily move back and forth.

Understand how to calculate the osmolarity of solutions. List which molecular properties of the solutes are important to consider when making these calculations (e.g. NaCl vs glucose)

(# of mol/L)*(# of particles ions dissociate into)

Map a generalized signaling pathway for G-protein coupled receptors. Give an example of a second messenger system that is activated by such a pathway and describe how this pathway can lead to a significant amplification of messages within a cell

*2nd messenger system*: protein kinase > phosphorylates protein that act as amplifiers

Understand how the activity of voltage-gated Na+ and K+ channels generates an action potential and the roles of these channels in each phase of the action potential (i.e. depolarization/rising phase, overshoot, repolarization, afterhyperpolarization/undershoot).

*Depolarization and rising phase*: Na and K channels begin to open, rapid entry of Na depolarizes *Overshoot*: Na channels close and slower K channels open *Repolarization*: K moves out of cell *Afterhyperpolarization*: More K out of cell causes hyperpolarization, K channels close and return to RMP

Contrast the generation and conduction of graded potentials with that of action potentials, identifying on the neuron the area in which each occurs.

*Graded potential* caused by ligand-gated ion channels, transient changes that occur in dendrites and synapse *Action potential* caused by voltage-gated ion channels, occur at axon hillock or first node of Ranvier in sensory neurons

Compare the distribution of ion channels along unmyelinated versus myelinated axons and explain how this accounts for the difference in conduction velocity between these two types of axons. Predict the effects on action potential propagation of demyelinating diseases, such as multiple sclerosis (CT 2.6).

*Myelinated axons*- leak channels are insulated by myelin leading to less loss of current flow and better conduction velocity. Ion channels only located at Nodes of Ranvier; thus signal has saltatory conduction along myelin sheaths and "jumps" and moves much quicker Demyelinating diseases: along locations where myelin sheath once was, current leak occurs and conduction slows. the signal cannot make it very far because it loses energy as it travels through the axon. *In an unmyelinated axon*, ion channels are sequentially placed all along axon; thus it takes longer send signal down axon. the energy isn't leaked out, it still contains the same signal, but it is simply slower. Distance between voltage gated channels needs to be small enough so local current flow can depolarize the membrane **Harder to generate action potential in demyelinating diseases **Axon diameter (bigger diameter = less resistance = faster current)

Differentiate between the properties of passive conduction of current within the cytoplasm of dendrites and axons (local current flow) versus the propagation of an action potential (CT 2.6).

*Passive conduction*: local current flow so depolarization can flow along axon. The stronger the initial amplitude, the farther the graded potential can spread before dying out; lost strength as they move through cytoplasm because of current leak via leak channels that allow positive ions to flow out of cell and because of cytoplasmic resistance *Propagation of action potential*: depolarization causes voltage gated Na+ and K+ channels to open and local current flow to initiates more voltage gated channels to open at next Node of Ranvier.

Explain how temporal and/or spatial summation of graded potentials (like postsynaptic potentials) occurs, and how these can trigger an action potential.

*Spatial summation* occurs when currents from nearly simultaneous graded potentials combine (separate synapses) *Temporal summation* occurs when two subthreshold potentials arrive at trigger zone within short period of time may sum and initiate action potential (same synapse)

Understand how the distribution of the various ion channels, transporters, and plasma membrane receptors determines the type of potentials and processes that take place in each part of a neuron and between neurons

*entire neuron*: what changes is the numerical value (more negative in some places and more positive in others due to ion concentrations/equilibriums) *-Graded potentials* occur in soma and dendrites of neuron; used for short distance communication *-Action potentials* occur down the axon of a neuron; used for long distance communication; require voltage-gated channels for Na, K, and Ca; also occur in presence of leak channels for Na and K (located down axon in addition to in the soma); local current flow occurs because of APs *-Ca influx/binding* and *neurotransmitter exocytosis* is caused by opening of voltage-gated Ca channels *-Neurotransmitter and Ca re-uptake* caused by Ca-ATPase *-Neurotransmitter binding to receptor proteins on postsynaptic neuron* causes AP to continue (VG Na channels open, depolarization starts, VG K channels open, repolarization/hyperpolarization starts)

List all of the different ways that ion channels on neurons can be gated (i.e. activated), give examples of each type of channel, and identify where each channel may be located

*voltage gated*: example are Ca channels in axon terminal that open when depolarization occurs, allowing Ca to flow in, bind to synaptic vessicles, cause exocytosis of vessicles, and ultimately lead to release of neurotransmitter *chemical gated*: examples are channels on the post-synaptic cell that open in response to ligand binding from neurotransmitter *mechanically gated*: example is sensory neurons in skin that react to pressure

Explain how the presence of approximately 150 mM NaCl (saline) can prevent osmotic swelling of cells in a solution that also contains a penetrating solute, such as urea

150 mM NaCl dissociates when dissolved, and therefore has an osmolarity of 300 mOsm. Since Na+ and Cl- are both non-penetrating ions, the extracellular concentration of np particles matches the intracellular concentration of np particles (300 mOsm). This results in no movement of water across the membrane to even out the concentrations. While penetrating solutes will cross the membrane to even out the concentrations, the change in volume is too minimal to have an affect on the cell volume

Know the typical value of intracellular osmolarity in human cells.

300 mOsm

Compare and contrast the properties of voltage-gated Na+ and K+ channels, and understand how voltage influences their activation and inactivation (do they both have inactivation gates?).

Both are activated by cell depolarization, play important roles in invitation and conduction of electrical signals They contrast: *Voltage gated Na*: two gates, activation gate closed at RMP, depolarization causes gate to open and Na enters cell, inactivation gate closes and Na entry stops, repolarization resets the gates. *Voltage gated K*: only has activation gate, at RMP activation gate is closed, depolarizing stimulus opens gate, K leaves cell, repolarization causes activation gate to close

Understand how the distribution of the various ion channels, transporters, and plasma membrane receptors determines the type of potentials and processes that take place in each part of a neuron and between neurons

CT 3.2

Explain how an increase in extracellular K+ concentration can have a dramatic effect on the EK, the resting membrane potential, and the neural and cardiovascular status of a person (CT 4.5).

Increase in extracellular [K] has larger effect because permeability of K ions is 30x that of Na. Also [K]out is relatively low to begin with and increase in [K]out causes bigger difference in ratio

Explain how the differential distribution of various transporter proteins to the apical or the basolateral epithelial cell membrane in the gut can lead to absorption of substances like water, Na, and glucose

Proteins on the *apical membrane* can bring in molecules against their gradient (due to active transport; i.e. glucose). Proteins on the *basolateral membrane* can then allow for the molecules to travel down their concentration gradients into the interstitium to therefore be absorbed. Na and glucose actively transported via apical membrane proteins, water follows via aquaporins to create equilibrium. Glucose converted to a different form within the cell and then diffused via facilitated diffusion on basolateral membrane into interstitium

Explain how the relative permeability of a cell to water and solutes can result in a change in cell volume

When the osmolarity of non-penetrating particles is not equal inside and outside the cell, the particles cannot move through the membrane to reach equilibrium. Therefore, water moves in or out of the cell (towards the area of low concentration) to try to dilute the particles so much that the concentrations are equal. This usually requires A LOT of water, which has a drastic change in the cell volume, whether it is entering or leaving the cell.