Chapter 3: The Neuronal Membrane at Rest
potassium channels
-4 subunits -selectivity determined by structures (pure loop - selectivity filter - arrangement amino acid residues lining pore regions of channel, and size of pore) -open when membrane is at REST
what mechanisms help the regulation of external K+ concentration
-BBB - limits movement of potassium into extracellular fluid of brain -astrocytes - potassium spatial buffer (membrane potassium pumps that concentrate K+ in cytosol and K+ channels)
ion pumps/active transporters
-NEEDS ATP to transport certain ions across membrane -ions travel AGAINST concentration gradient (LOW to HIGH - active transport) - opposite direction helps maintain membrane stability -helps to create ion concentration gradients
ionic driving force information
-RMP (at a steady state) is DIFFERENT from equilibrium potential (EP) for an ion -at RMP, net flux of given species of ions will NOT be zero, as membrane would not be at ion's EP (driving force will be on ion, causing it to move in/out of the cell if channels are open) -ions driven across membrane at rate proportional to the difference b/w the membrane potential and the equilibrium potential (Vm-Eion) for particular ion
electrical potential
-aka voltage -units: (volts) -force exerted on charged particle -difference in charge b/w anode and cathode -symbol = V
sodium potassium pump
-an enzyme -70% of total ATP used by brain is used by this pump how it works: -uses active transport (ATP required - against gradient) -breaks down ATP -chemical energy released by ATP breakdown process - DRIVES PUMP -internal Na+ exchanged for external K+ (2 K+ enter for every 3 Na+ out - helps maintain gradient) -# of positive ions out is more than in, pump contributes small NEGATIVE charge to RMP *needs ATP b/c ACTIVE transport - sends ions AGAINST concentration gradient (low to high)*
polarity of water
-bonds within/between water molecules are POLAR COVALENT between hydrogen and oxygen (electrons are SHARED UNEQUALLY) -oxygen is electronegative - pulls electrons toward itself due to uneven distribution of electrical charge leads to charge separation and polarization of electric charge of molecule (makes O2 partially NEGATIVE and H2 partially POSITIVE) -hydrogen bonds can form between 2 water molecules *greater polarity = stronger hydrogen bonds*
what do amino acids have in common
-central carbon -carboxyl group -amino group -covalent bonds
basic amino acid structure
-central carbon atom (alpha carbon) -4 covalent bonds (H+ atom, NH3+ - amino group, COO- - carboxyl group, and R group - variable group) -R group changes with every amino acid
ion channels
-channels with subunits and pore (hole ions travel through) -ion selectivity (selectively permeable for certain ions) -allow ions to diffuse DOWN concentration gradient (HIGH to LOW - passive transport) - NO ATP needed -may be gated
ion movement is driven by ___
-concentration gradient (diffusion - needs channel to pass through) -electrical gradient *both generate membrane potential* also determined by membrane permiability
chemical components involved in generating membrane potential
-cytosol -extracellular fluid -phospholipid membrane -proteins spanning membrane
factors affecting current flow
-electrical potential -resistance -conductance
microelectrode
-filled with conductive solution that penetrates neuronal membrane with minimal damage -connected to a voltmeter (measures the difference in electrical potential between tip of the electrode and wire placed outside) *uneven electrical charge across the membrane - inside relatively negative compared to the outside*
Goldman Equation
-formula used to calculate RMP -takes into account relative permeability of membrane to DIFFERENT ions (at rest) - ex: if neuronal membrane only permeable to K+ ions, membrane potential = POSITIVE Vm = RT/F * ln(Pk[K+]o + PNa[Na+]o/Pk[K+]i + PNa[Na+]i) OR Vm = RT/F * ln(Pk[K+]o + PNa[Na+]o + PCl[Cl-]i/Pk[K+]i + PNa[Na+]i + PCl[Cl-]o)
proteins spanning phospholipid membrane
-high ion concentration on both sides - proteins provide routes for ions to cross membrane through -ALLOW ion movement (mem. blocks, proteins allow) -ions form (cause) potential types: -ion channels -ion pumps/active transporters
two compartment model of a neuron
-inside separated from outside by phospholipid membrane that does NOT allow ions through b/c charged ions only travel through hydrophilic environments -inside cell = salt -A- ions = any molecules wit negative charges -K+ and A- ion concentration greater INSIDE of cell (charges are equal - solutions are electrically neutral) -K+ ion channels allow K+ to travel down concentration gradient (now negatively charged inside of cell) -inside = more negative - K+ ions get pulled back in -equilibrium is reached *equilibrium state is reached when number of ions going in balances the number of ions going out*
electrical gradient
-ions are attracted to areas of opposite charge (+ to -, - to +) - LIKE charges REPEL (need close proximity to attract, but it takes strong forces and energy to keep them apart) -induces net movement of ions in solution using ELECTRICAL field -ex: cathodes and anodes (Na+ attracted to negative cathode, Cl- attracted to positive anode) -has electrical current
factors affecting resistance
-length -thickness -temperature
phospholipid membrane
-membrane of a cell made from phospholipid molecules and proteins -hydrophilic head (charged), hydrophobic tail (neutral) -membrane BLOCKS substances from entering, proteins ALLOW substances through that they code for (selective permeability)
conductance
-opposite of resistance - ability of particles to migrate from one point to another -symbol = g -units = S -depends on number of ions/electrons available to carry charge and ease with which charged particles can travel through space
special properties of water (related to cytosol and extracellular fluid)
-polar -liquid @ room temp -good solvent (UNIVERSAL) -water and ions in salty solution help generate membrane potential
4 levels of protein stucture
-primary -secondary -tertiary -quaternary
resistance
-relative inability of electrical charges to migrate -units: ohms -calculated by equation: R = 1/g (conductance) - as resistance increases, conductance decreases and vice versa (inverse relationship) -symbol = R
current
-unit of measurement in amps -symbol = I
Nerst equation
-used to calculate exact value of equilibrium potential (mV) permeable to only ONE ion -based on physical chemistry principles -takes into account temperature (higher the temp, faster it dissolves), charge of ion, and ratio of external/internal ion concentrations Ex = RT/zF (ln) [X]out/[X]in
communication steps within nervous system
1. collect 2. distribute 3. integrate 4. act *neurons conduct info over LONG distance using ELECTRICAL SIGNALS*
principles of electrochemical equilibrium
1. ions affected by BOTH electrical (charge) and chemical (concentration) gradients 2. chemical gradient and ion movement INDEPENDENT of concentrations of other ions 3. electrical gradient is DEPENDENT on all charges within the cell (exerts equivalent effect on all ions - all ions dependent on charges within cell) 4. each ion has its OWN equilibrium potential (equal # of ions entering/leaving cell - concentration can still be higher/lower on either side when this is reached)
how many different amino acids are there
20
a peptide bond is a ____ bond
COVALENT
which has a higher driving force, Na or Ca?
Ca
ionic driving force equation
E = Vm - E(element symbol and charge) - negative ions move INTO the cell, positive ions move OUT of the cell (if answer is neg/pos, this is what the ion will be doing)
Calcium (Ca+) concentration is _____ inside/outside of cell
HIGHER on outside, LOWER on inside
Chlorine (Cl-) concentration is _____ inside/outside of cell
HIGHER on outside, LOWER on inside
Potassium (K+) concentration is ____ inside/outside of the cell
HIGHER on the inside, LOWER on the outside
Sodium (Na+) concentration is ____ inside/outside of the cell
HIGHER on the outside, LOWER on the inside
neuronal membranes are most permeable to what ion and why
K+ because of the leaky ion channels (open when membrane potential is at rest) also slightly permeable to Na+ and Cl- - ions influence RMP to a small degree
banana in salty milk pool
K+ higher on inside, Na+, Ca+, and Cl- higher on outside of cell
death by lethal injection
KCL given intravenously (directly into blood stream through veins) increases K+ concentration outside of cell (neurons in brain protected from this b/c of BBB, other body cells, like muscle cells, aren't) *without neg. RMP, cardiac muscles cannot generate impulses needed for contraction, which is what makes it lethal, as the heart will stop beating*
2 functions performed by proteins in neuronal membrane to establish/maintain RMP
Provide channels that control the movement of specific ions across the neuronal membrane Pump sodium and potassium ions across the membrane against their concentration gradient to maintain the resting membrane potential
when is the RMP close to the equilibrium potential and when does the EP influence the RMP?
RMP = close to EP for the ion that carries the majority of the resting current for neurons (K+ closer than Na+) EP for a particular ion will ONLY influence the RMP if the membrane is PERMEABLE to that ion
membrane potential changes caused by ____
SMALL changes in ion concentration (b/c # of ions crossing is very small)
when membrane is at potassium equilibrium potential, which direction is the net movement of potassium ions (in/out)
The potassium equilibrium potential represents a balance between the chemical and electrical forces driving potassium across the membrane through potassium channels. There is no net movement of potassium ions at potassium's equilibrium potential, which is -80mV
water as a polar solvent
UNIVERSAL SOLVENT - most substances can dissolve in it -ex: NaCl (Na+ = cation, Cl- = anion - H+ attracted to Cl-, O- attracted to Na+ - pulls compound apart, which is why/how it dissolves - charged portions of the water molecule have a stronger attraction for the NaCl ions than the NaCl ions have for each other)
T
absolute temperature (K)
Calcium pump
actively transports Ca OUT of cytosol across the membrane
protein shape and function are intricately linked, meaning?
any change in shape caused by changes in temperature or pH may lead to protein denaturation and a loss in function
phospholipids
building blocks of membrane -phospho = polar phosphate group (forms hydrophilic head) -lipid = fatty acids (non-polar chain of hydrocarbons forming hydrophobic tail) forms barrier to water-soluble ions and water (PREVENTS ion movement)
depolarization
change in membrane potential from resting (-65mV) to a less negative value (-30mV - example) example: increasing extracellular potassium = depolarization of neurons
electrochemical equillibrium
chemical driving force is balanced by electrical driving force potential change across membrane offsets concentration gradient
molecules are assembled from what
combinations of amino acids
chemical driving force
concentration gradient
[X]in
concentration of cell INSIDE of membrane
[X]out
concentration of ion OUTSIDE of membrane
as resistance increases, what happens to the current?
current decreases
as voltage increases, what happens to the current?
current increases
movement is ____ on membrane permeability
dependent
ionic driving force
difference between real membrane potential and equilibrium potential for particular ion (difference causes pull on K+, which causes driving force)
equilibrium potential
electrical potential difference across cell membrane that balances concentration gradient for an ION net flux of ion = ZERO (happens at -80mV - inside relative to outside of cell) if membrane potential is only permeable to ONE ion, membrane potential is equilibrium potential for that ion equilibrium potential relates to SINGLE ion, membrane potential relates to ALL ions *equilibrium potential FOR AN ION is the steady electrical potential that would occur if the membrane was permeable only to that ion*
Ex
equilibrium potential
F
faraday constant
pore loop
folded chain of amino acids that help make the channel selective toward K+ due to the amino acid properties (R group) makes a hairpin turn within the plane of the membrane
how length affects resistance
greater the length, higher the resistance (longer = higher - L increase, R increase)
tertiary structure
helix/pleat fold into 3D structure (caused by side chain reactions)
how temperature affects resistance
higher the temperature, higher the resistance (hotter = higher - temp increase, R increase)
regulation of external K+ concentration
importance: neuronal membrane at rest is MOST permeable to K+ ions (for stable maintenance of membrane) -membrane potential closer to EK -membrane potential sensitive to changes in K+ ion concentrations outside of cell (changes voltage drastically) INCREASE in extracellular potassium changes membrane potential - causes depolarization of cell (makes it LESS NEGATIVE) *when K+ outside and inside are the SAME - neuron function would change because there would be a change in membrane potential*
room temperature water is a LIQUID
important for cell as it serves as the fluid medium for ions to move around (conduct info) and for cell structure (chemical reactions) can form bonds between ANY element located in group 16 (oxygen, sulfur, etc)
cytosol
inside of cell - salty fluid (water and ions in solution)
what helps maintain the concentration gradient
ion pumps (constant input/output (exchange) of a specific (fixed) amount of ions)
what makes a membrane permeable to a certain ion
ion selectivity (pumps letting only certain ions through)
ionic bonds
ions held together by attraction of opposite charges (equally shared/transferred)
ion weight is determined by ___
membrane permeability towards that ion
positive current
movement in direction of positive charge
what causes current
movement of electrical ions
electrical current
movement of electrical ions (charges)
diffusion
movement of particles down a concentration gradient (high to low) - molecules distribute UNIFORMLY -requires channels for ions to pass through -NO ATP -equal distribution of ions = NO NET MOVEMENT (b/c both sides are at equillibrium)
quaternary structure
multiple subunits (polypeptide chains) come together (protein consisting of 1+ amino acid chain)
ln
natural log (log to base e)
anion
negatively charged ion
cytosol and extracellular fluid are both electrically ___
neutral
on which side of the neuronal membrane are Na+ ions more abundant
outside
extracellular fluid
outside of cell (surrounds it) - salty fluid (water and ions in solution)
polypeptides
polymers composed of amino acids
primary structure
polypeptide chain (amino strand)
secondary structure
polypeptide chain folds into either alpha (a) helix or beta (b) pleated sheet (caused by hydrogen bonding of peptide backbone)
cation
positively charged ion
electrical driving force
potential difference across membrane
membrane potential
refers to separation of electrical charge across plasma membrane (difference in electrical charge between inside and outside of cell - created due to unequal distribution of ions on both sides of membrane) -symbol = Vm
ohm's law
relationship between voltage, current, and resistance equation: V=IR (if conductance instead of resistance, formula: V=I/g) I=V/R R=V/I *volts are trying to push current through, resistance is trying to prevent that *NO channels = NO membrane potential changes* (if I=0, V=0)
at a constant velocity, what happens to the resistance and the current?
resistance increases, but current decreases
how thickness affects resistance
smaller the diameter, greater the resistance (thicker = lower - thick increase, R decrease)
stages of ion movement example
stage 1: no passage (no proteins) stage 2: only cation passage (one way) - only cation channel (inside of cell now MORE NEGATIVE b/c cations are LEAVING) stage 3: only cation passage (both ways) - cations pulled back to inside due to charge attraction (NO NET FLUX b/c amount leaving = amount entering - balanced)
RMP is also called
steady state - weighted average of individual equilibrium potentials
R
universal gas constant
z
valence (electrical charge) of ion
unit for electrical charge
volts
hydrophobic
water FEARING (ex: non-polar molecules like lipids, but not all non-polar substances) -repel water molecules -do NOT interact with/dissolve in water
hydrophilic
water LOVING (ex: ions and polar molecules) -attracts water molecules -interact with/dissolve in water
resting membrane potential/resting potential (RMP)
when cell is NOT generating impulses/action potentials (not signaling) - inside of membrane has NEGATIVE electrical charge compared to outside (difference is referred to as RMP) ALL cells have this used for transmitting signals between different parts of cell in electrically excitable cells (can trigger potential b/c of membrane potential - have excitable membranes)
when can you calculate the equilibrium potential
when you know the concentration difference across the membrane