Meeting 14 & 15

E_(ion) = RT/ZF*(ln)[ion_ext]/[ion_intra]

• -R=gas constant (8.31 K^-1mol^-1)
• -T=abs. temp (293 K @ 20 C)
• -Z= charge of ion
• -F= Faraday constant (23062 cal/mol*V)

• -inside: potassium (K+)
• -outside: sodium (Na+)
• 
• -Cl- (as you can see) is mostly outside the cell; the major negative ion INSIDE the cell is P- (from organic molecules)

-resting potential depends mostly on K+: -70 mV

E_m - E_Na = equilibrium potentials (solve for these using Nernst?)

-membrane potential is due to overall the ion interactions together; if there’s NO conductance for an ion, it means the membrane isn’t permeable to it; this ion doesn’t contribute to membrane potential

• -low conductance: will contribute, but not that much
• -high conductance: membrane is WIDE open to transport of an ion

(the ease at which an electric current passes [opposite of resistance]; G=I/V)

you can close or open ion channels

-opening channels increases conductance (inevitably)

• -happens when you increase membrane permeability to Na+
• -change in a cell's membrane potential, making it more positive (aka less negative)

• -happens when you increase permeability to K+
• -a change in a cell's membrane potential that makes it more negative
• -opposite of depolarization
• -is often caused by efflux of K+ (a cation) through K+ channels, or influx of Cl– (an anion) through Cl– channels

•the concentration of ions on either side of the membrane

-only thing that matters is the permeability of the membrane to Na & K, (Cl & Ca too) and HOW MUCH they LET ions go through; not how many ions go through

• -the selective permeability of the membrane to K+ via potassium channels
• -BUT significant energy is stored in the Na+ gradient

ΔG = ΔG_c + ΔGm

ΔGc = RT* (ln) [ions out]/[ion in]

• ΔGm = FE
• F=faraday constant
• E=membrane electric potential (usually -70mV)

-if overall free energy change is NEGative, then there's spontaneous movement of the ion inside the cell

• 
• -at equilibrium

• •ANALOG: found in small animals where signal doesn't have to travel very far
• -aka graded local potentials
• -more signal there is, the more a cell will depolarize
• -analogy = LP (sound fades, progogation of signal decays with distance)

• •DIGITAL: useful for larger animals
• -aka action potentials
• -as you increase the signal, the height of the peaks doesn't increases, the FREQUENCYof the peaks increase
• -low signal level --- low frequency, HIGH signal ---HIGH frequency
• -they're either completely there or NOT
• -analogy = iPod; music is always there

-ropagation of digital information/signal is more robust than analog signal

TTX: blocks action potentials in nerves by binding to (voltage-gated) sodium channels, preventing nerve cells from firing; lose inward Na+ current --- cannot have action potential (no depolarization

TEA: blocks action potentials in nerves by binding to (voltage-gated) potassium channels, preventing nerve cells from firing; lose outward K+ current --- no action potential (aka hyperpolarization)

-sequential changes in Na+ and K+ Permeability

• -rising (ascending) phase of an action potential comes from the opening of Na+ channels
• -falling phase comes from inactivation of Na+ channels and opening of K+ channels
• -timing is crucial: Na+ channels must open BEFORE K+ channels

the [Na+] (concentraiton) of sodium inside the cell doesn't SIGNIFCANTLY. CHANGE. Number of ions that migrate in is insignificant (Na/K ATP-pump help equilibriate)

-action potential is in no way due to a change in CONCENTRATION of Na or K

• -highly selective
• -very fast
• -voltage sensitive
• -have a mechanism for rapid inactivation: cannot stay open forever

• (1) changes in membrane potential: voltage-gated channels
• e.g. Shaker K+ channel

• (2) ligand binding: ligand-gated channels
• e.g. Ach receptor

• (3) mechanical forces: sensory receptors
• e.g. mechanosensitivechannels

• (4) channels can be permanently open
• e.g. open rectifier K+ channels

• •-40 mV; the Na+ channel likes it and opens & the membrane channel is depolarized
• 

• -voltage-gated Na+ channels open when membrane depolarization reaches threshold (~ -40 mV???)
• -opening of Na+ channels = further depolarization
• -this makes the Na+ channels open larger
• -opening of Na+ channels/depolarization = autocatalytic
• -when Na+ channels are fully opened: membrane potential becomes close to Na+ potential (~ +50mV)

-voltage-gated K+ channels have the same properties but they lead to negative feedback; their opening leads to repolarization and therefore their own closing

• -Na+ ions are _smaller than K+ ions; so how do K+ channels prevent Na+ ions from entering?
• -the ability to selectively filter comes from backbone carboyl oxygen on residues in the P segement of the channel
• -as K+ enters the channel, it becomes dehydrated (loses bound water molecules from the extracellular fluid) but they're replaced by binding of the 8 carbonyl oxygens inside the channel [btw, it's easier to remove water molecules from K+ than Na+, b/c it's a larger molecule w/ more layers]

• -a dehydrated Na+ ion is TOO SMALL to bind all 8 carbonyl oxygens in the channel, therefore they prefer to remain in water in their original conformation
• -the same is true for Ca2+ ions

• -the smaller the ion, the MORE energy is takes to REMOVE the water from the ion
• -in the small ion, the water molecules get closer to the nucleus, making the attraction stronger

• -K+ ion: 133 Å
• -Na+ ion size: 95 Å

• -so the channel opens, changing the inside of the cell from negative to positive
• -the ball is made up of molecules with lots of positive charge
• -understanding that most channels are amphipathic (aka hydrophobic when interacting with membrane fats but polar/hydrophilic on the inside of the poor and on the extracellular side), we know the inside of the pore is negative charged
• -this negatively charged pore attracts the positively charged ball (especially because after depolarization the inside of the cell is now positive) causing it to be blocked from the inside
• -leads to an inactivated conformation, not closed

-Na channel deactivates itself using this mechanism; triggered by a strong depolarization