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I remember the lecture that Brons did on this material. He covered the sodium potassium pump, which I had thought i somewhat understood, but he was able to completely muddy the waters. He took a simple mechanism and spent 1.5 hours confusing it. So here I will summarize my notes and previous knowledge, and see if I can get it to make sense again.


The Sodium Potassium Pump, aka Na+/K+ ATP-ase, maintains the membrane potential in all the cells in the body. The Na/K pump creates about -10mv (a fraction of the total potential). Each cycle of the pump takes 3 sodium ions OUT of the cell, and 2 potassiums in. Both ions are positive but since more Na+ is going out than K+ is coming in, the cell becomes negatively charged inside.

The steps in the Na/K pump cycle:
1. Na+ binds
2. ATP --> ADP leaving its phosphate on the ion channel, causing a conformation change in the protein, Na+ is released on the other side.
3. K+ binds, phosphate group is released.
4. Protein shifts back to earlier conformation, K+ is released.

Membrane Potential: The total resting potential is usually in the neighborhood of -90 to -55 millivolts. Abundant ungated "leakage" K+ channels make the membrane permeable to K+. The Na/K pump creates a K+ concentration gradient that makes K+ want to leave the cell, so it can flow out of the cell against the potential, increasing the negative charge. It is simultaneously pulled into the cell by the electrical gradient. The net flux for K+ is high; it gets around.

Leakage channels:
--The most ubiquitous K+ channels are "leakage channels" which are non-gated but flicker between open and closed. ??
--Brons says the K+ channels are "the primary determinant of resting membrane potential".
--aka: Two-pore-domain potassium channels: This family of 15 members form what is known as "leak channels" which possess Goldman-Hodgkin-Katz (open) rectification.
--regulated by several mechanisms including oxygen tension, pH, mechanical stretch, and G-proteins
--name is derived from the fact that the α subunits consist of four transmembrane segments, each containing two pore loops. As such, they structurally correspond to two inward-rectifier α subunits and thus form dimers in the membrane.
--all kinds of channels can be up- or down-regulated--changing the number or permeability of the channels.

Na+ can't flow passively through any pores, it's kept outside the cell until specific channels let it in. So the Na+ net flux is low. Equilibrium is reached when the inward and outward flows of K+ are equal, or 'steady state'.

Voltage gated channels are the ones that let Na+ into the cell. In nerve or muscle cells this depolarization can generate an action potential.

ION FLUX = "the passage of ions through ion-specific, cylindrical, membrane protein based channel". Ion specificity of a channel depends on the distribution of charges in the protein, and the diameter and shape of the channel.

permeability = how easily something can get across the membrane. Gating properties of channels dictate this. Three main types of gates: physically gated, ligand/transmitter gated, and voltage gated.

E is a symbol for equilibrium potential, which is theoretical. The formula looks familiar. Bron's comments about it are total gibberish. Surfing the internet for insight reveals that Brons was translating something fairly simple into gobbledy gook. Equilibrium potential comes from a complex formula that takes the natural log of concentration of ion moving out over concentration of the same ion moving in. You have a different E for different ions, depending on their flow.

Vm is the total membrane potential, generated by the net flux of all ions, and measurable. Goldman equation quantifies Vm by weighting ionic flux against permeability. To change the membrane potential and hence the excitability of a post synaptic cell, change one of the two variables in the Goldmann equation: resting potential or channel permeability. Change resting potential by changing ion concentrations, esp K+ or Ca++. Change channel permeability by changing the sensitivity of voltage gated Na+ channels to depolarizing current (this is how lydocaine the painkiller works).

net flux = net driving force x permeability

net driving force = sum force on a given ion, found by combining concentration and electrical gradients

In nervous tissue, glial cells have support functions. Schwann cells in the PNS wrap their membranes around nerve axons, creating the myelin sheath. Each cell-wrap is separated by a node of Ranvier, where action potentials are generated.

PSP = postsynaptic potentials

EPSP = excitatory post synaptic potential --- a graded response, in balance with IPSPs (inhibitory)---forms an AP only if there's enough excitatory's to overwhelm the inhibitory's.

AP = action potential, all or none electrical cascade that happens only when the E and I PSPs accumulate in such a way to make the nerve reach threshhold

afferent = coming toward the CNS

efferent = going out from the CNS

depolarization = Na+ channels are activated, Na+ flows in w/ high driving force, reducing the polarization of the membrane and possibly triggering an AP. Membrane "nearly reaches Na+ equilibrium potential for Na+ at peak of action potential"

hyperpolarization = membrane potential is more than -60mv = refractory period, two kinds, absolute and relative. Relative: nerve is hard to fire again. Absolute: channels cannot be reactivated. Leakage K+ channels not part of this system.

myelinated axon conducts action potential faster because saltatory conduct doesn't have to wait for so many channels to open and close. The electrical pulse travelling along the axon jumps across the sections of axon that are myelinated because the myelin insulates the axon and won't let the ions leak around, thus propagating the charge.

continuous propagation limits conduction velocity but maintains fidelity.

demyelination is a common cause of neuropathy, esp in autoimmune conditions like MS and Guillain-Barre syndrome. Glial called unwind and myelin thickness decreases, current leaks out and AP's are lost.

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