Membrane Electrophysiology & RMP

What is the resting membrane potential (RMP) of the membrane and why?

-The RMP is close to -70mV. -The reason being that K+ is more permeable(more leak channels) than Na. K+ potential is -90mV. and is leaving the cell. -The more k+ that leaves the more negative it will become. The potential of Na is +60mV. But since the cell isn't as permeable to Na coming into the cell, the cell stays closer to the k+ potential.

The membrane potential line moves towards

-The ion that has more open ions, driving force -Only way to change Ek is thru concentration

What would happen to the membrane potential line if a ton of Na+ channels opened?

Becomes less negative

T/F: Neurons are polarized

True

When are the equilibrium potential (Ek) and RMP(Vm) the same for K+?

*Only the same* when that cell only has leak channels for K+ and no other ions can cross the membrane at rest.

In which way does the Na/K ATPase move?

-3 Na+ out -2K+ in

What is the Equilibrium potential? (Ex)

-Also called the Nernst potential. It is the potential at which the potentials are the same on both sides and are therefore no longer moving. Does not include concentration. -for a particular ion, is the amount charge (measured in mV) found on the *inside* of the membrane when the net movement of that ion is zero (when [gradient] and electrical gradients are at equilibrium).

What is depolarization/repolarization/hyperpolarization?

-Depolarization: is the potential becoming less negative -Repolarization: The potential becomes more negative, returning to RMP -Hyperpolarization: Overshoot of RMP, becomes a smidge more negative than RMP

What is the resting membrane potential?

-Difference in electrical charge across the membrane at rest -No change in negative or positive charge inside or outside -The amount of negative charge found on the inside of the cell membrane when the concentration gradient and the electrical gradients for all ions with open channels are equal is the resting membrane potential (Vm)

Anytime potassium, which is positevely charge, goes *agaisnt* its concentration gradient, and goes back in to pair with a negative ion, it is following its:

-Electrical gradient

How will the membrane potential change with an increased number of Na+/K+ pumps on the cell membrane?

-Greater gradient -AP will be stronger -RMP may be slightly lower

What cause the negative membrane potential inside the cell?

-Leak channels -Na+/K+ ATPase, cause net charge of -1 inside the cell

What happens during hyperkalemia to cells?

-Less of a driving force since you have more K+ outside -Cause the cell to be less negative or more positive -Leads to depolarization -If it gets really bad, it will reverse the concentration

How does hypernatremia effect RMP?

-Little effect on RMP

How will the membrane potential change when a cell begins to express a small number of Cl- leak channels on it's membrane?

-More chloride outside originally -Chloride's concentration gradient will drive chloride into the cell if chloride channels open -When the concentration gradient and electrical gradient for chloride reach equilibrium the cell will have a new lower RMP that will be lower than it was before the chloride leak channels opened due to the extra negative charges brought inside the cell.

What type of cells of capable of sending signals (action potentials?)

-Only cells that can generate and maintain a consistent resting membrane voltage (steady state) -Interruptions in the resting membrane voltage of a cell (depolarization) are usually elicited purposefully by the body for the purpose of sending signals

Know which ions are high outside and inside

-Only ion that is high inside is K+ -Driving force for all others is towards the inside of the cell

DO NOT need to memorize these, i just find it helps in knowing concentration gradients of Na+/K+/Ca2+/Cl-

-Only thing that is high intracellularly is K+

When is the resting membrane potential reached?

-When the concentration gradient and the electrical gradient for K+ are at equilibrium with each other (assuming only K+ channels are open on that cell at rest).

Ouabain is a poison that was traditionally used in east Africa to poison the tips of arrows for hunting or warfare purposes. Ouabain is a Na+/K+ ATPase pump inhibitor that causes muscle paralysis by affecting motor neurons. 1)Do you think this poison would affect the function of motor neurons quickly (within seconds) or slowly (within several minutes or longer) in its victims? 2)Describe the molecular mechanism that supports your answer.

-Within minutes, You start with a very large gradient so you will need to release many action potentials to stop the concentration gradient. -Blocking leak channels would be much faster, since you have a build up of positive ions inside the cell that will not leave

Review: C BIG KK, treatment for hyperkalemia

1)Calcium -Stabilizes cardiac electrical activity -Does not lower K 2)Beta-2 agonist and/or bicarb(albuterol) -B2 increases Na-K ATPase and results in K movement into the cell 3)Bicarb raises pH and therefore promotes K movement into cells 4)Insulin -Increases Na-K ATPase (take up excess K after a meal) 5)Glucose -Given with the insulin to prevent hypoglycemia 6)Kayexelate -Binds K in the GI tract (takes hours-days to work) Dialysis(take K away) Diuretics(furosemide/thiazide)

Rate of an ion movement is dependent on what 3 things?

1)Concentrations of a given ion separated by a permeable barrier 2)Membrane potential (electrical gradients) 3)Dynamic permeability (number of open channels) of the membrane to that ion

What effects the number of open channels?

1)Hydrophobic bilayer = highly resistant to ion flow 2)Ion channels = molecular conductors; lower resistance 3)Many physiological factors can open/close channels to change membrane potentials -Endocrine signals (ligand gated channels) -Neuromodulation (ligand gated/ voltage gated) -Physical stimuli (mechanically gated) touch, light, pain *(an open channel does not necessarily always conduct ions -need a driving force)

What generates resting membrane potentials? What do motor neurons allow for?

1)Motor neurons generate resting membrane potentials 2)Motor neurons allow for both voluntary and involuntary muscular contraction via action potentials. Action potentials are not possible without resting membrane potentials.

If the resting membrane potential (Vm) is given & the Nernst equation is used to calculate the equilibrium potential of an ion (Ex), the following conclusions can be drawn:

1)The difference between Ex and Vm = the net force of that ion 2)If Ex = Vm, the [gradient] and electrical gradient for that ion are at equilibrium with each other and the net movement of that ion will be 0 = steady voltage reading across membrane 3)If Ex ≠ Vm, the gradients for that ion are not at equilibrium = There will be a net diffusion of that ion if its channels are open 4)An ion will always diffuse in the direction that brings the membrane potential (Vm) toward its Ex if channels are open until an equilibrium is reached 5)The Rate of ion diffusion is directly proportional to the net force & membrane conductance (g) of that particular ion 6)As an ion diffuses & the Vm approaches Ex and the net force is decreased

Review: Electrical gradients

1. Magnetic attraction or repulsion across a cell membrane created by unpaired charged ions 2.Unequal build up of any charged ion on either side of the membrane can create or effect an electrical gradient across a membrane, (-) and (+) ions are attracted to each other 3.Because most ion channels separate the (-) ion from the (+) ion and only allow one type of charged ion through its pore, concentration gradients will always cause separation of charge. That will eventually trigger the formation of an electrical gradient 4.Electrical gradients oppose concentration gradients, the two eventually reach equilibrium together

Review: Concentration/chemical gradients

1.Each type of ion has it's own concentration gradient that is unaffected by other ion gradients 2.The [gradients] for Na+ and K+ are created by the Na+/K+ ATPase Pump 3.Ions (of one charge type) flow through leak channels from [high] to [low] 4.At rest, most cells are largely only permeable to K+, therefore the K+ [gradient] has the LARGEST effect on a cells Vm = Don't mess up [k+] in IVs and monitor patients with conditions that cause [K+] imbalances carefully!

Describe the steps of an action potential

An action potential opens it's voltage-gated Na channel rushing Na in, which once it reaches threshold will depolarize. The V.G Na channel will quickly close, meanwhile the V.G k+ channels open slowly, allowing k+ to leave, as well as the leak channels, bringing the potential down. to the RMP, called repolarization. However since the K+ also close slowly, it will cause the potential to go below the RMP, hyperpolarizing

What is an electrical gradient

Difference in electrical charges between the inside and outside of the cell

What happens to the equilibrium potential and RMP for K+ if more than one ion can cross the cell membrane?

If more than one type of ion can cross a cell's membrane at rest than the equilibrium potential for K+ will not be that cells Vm.

How will the membrane potential change with a downregulation of K+ leak channels on the cell membrane?

Less potassium efflux = less build up of negative charge on the inside of the membrane = more positive RMP

What effect does hypercalcemia have on the RMP?

Little effect on RMP

What effect does hyperchloremia have on the RMP of cells?

Little effect on RMP

What happens during hypokalemia to cells?

Mason explanation: -Too much K+ inside the cell, will lead to excessive release of K+ due to the increase in driving force -Cause hyperpolarization of neurons, too negative inside the cell -*Insulin, epinephrine, aldosterone promote cellular uptake of K+ Lacies explanation: -Too little K+ outside the cell, will cause an increase in driving force from the outside to inside. K+ Will rush out and leave more negative charge inside the cell, leading to hyperpolarization

If K+ permeability goes up the neuron get more negative or less negative?

More negative

If the number of leak channels increase for k+ does the RMP get more negative or less negative?

More negative

What establishes the concentration gradient on the membrane?

Na/K+ ATPase

Know how to use the nernst equation

Nernst equation -Positively charged are outside/inside -Negatively charged ions are inside over outside Goldmann equation -Positively charged ions are Inside/outside -Negatively charged ions are Outside/inside Picture is showing goldmann's equation

What is a limiting factor with ion channels?

Saturation

T/F: Only leak channels can change the RMP

True, in contrast dynamic permeability (how many channels are open) change the membrane potential

What happens under steady state (resting) conditions?

Under steady state (resting) conditions (no new channels open or close) the electrical gradient for an ion will have "catch up" with it's concentration gradient and the two will reach equilibrium. The net movement of charges across the membrane will then be zero.