M101 A Lec

ion channels, regulate flow of ions and control electrical signals in neurons

cell membrane potential (or resting), store electrical energy due to uneven distribution of ions across membrane

acts as a capacitor that can seperate charges to create membrane potential

no net flow of ions across membrane (resting) or when membrane is at equilibrium potential for specific ion

no change in voltage

open or closed

I r (ionic current) is equal and opposite to Ic

FALSE

depending on channel can be Na+, K+, Ca2+

TRUE

either conducting (open) or not conducting (closed)

1. channel needs to be conducting (open to allow ions to flow)

2. needs driving force (V_m-Eion): difference between membrane potential (Vm) & equilibrium potential for ion (E ion), if there's difference ions move through channel generating current

depolarization (less neg)

inward (ions moving into cell)

negative (movement of pos ions considered neg current)

a: rate constant for channel opening

b: rate constant for channel closing

voltage clamp

current across membane

1. Both measure ionic currents & used to control membrane potential of cell

2. voltage clamp records I_total from many channels (macroscopic current)

3. Patch clamp is single channel recording, measures current through individual ion channels (microscopic current)

Difusssion: movement of ions from high to low concentration

Active transporter: move against concentration gradient, requiring ATP

Passive transporter: move without energy input (facilitated diffusion)

depends on energy source which can come from cellular metabolism or electrochemical gradient

Uncharged molecs are sensitive to concentrations.

If not equally distributed, they will move to equal concentrations, creating osmotic pressure that drives their movement.

ion sense electrical and concentration gradients. Nerst equation calcs voltage at which both forces (electrical & concentration) balance

- if ions equally distributed, Nerst potential is zero

- if ion move out = ion move in --> no net movement

the conformation of a protein can switch between states: open, closed, or random (stochastic). any moment, there's a probability of finding molecules in given state

At Nernst potential, there is no net movement of charge for that specific ion; the driving forces driving the ion in and out are equal, in a balanced state.

Nernst potential shifts the zero current potential from 0V to equilibrium potential of the ion (E_ion)

I _ion = G_ion (V-E_ion)

individual ion currents add up to each other, total curent is sum of all ion currents.

large family of proteins that control ion flow across membrane

have 6 transmembrane (TM) domains and a pore forming loop between TM5 and TM6. function by forming tetramers (four subunits)

a. K+ and Na+ channels contain multiple subunits, with each subunit consisting

of repeating transmembrane spanning motifs

b. K+ and Na+ channels differ in the selectivity filters, conferring selectivity to K+

and Na+, respectively

c. For example, K+ channels have a signature amino acid sequence that is

highly conserved and forms the selectivity filter

protein that helps form the structure that let ions pass through membrane

protein helps create the actual opening (pore) through which ions flow, splits transmembrane domains in 2 and lines the channel to let specific ions pass

5th and 6th transmembrane domains of protein

Na+, Ca2+ is similar to K+ channels. In these channels, there are four k channels like domains that make up full channel, instead of being 4 seperate proteins, Ca2+ and Na+ are part of one single protein rather than 4 seperate proteins coming together.

domain TM4

alpha 1. most channels have interacting proteins or subunits

The behavior of individual ion channels determines the overall flow of current across the membrane. Current can either charge or discharge the membrane's capacitance, changing the membrane voltage.

charged, voltage across membrane increases. discharge, voltage decreases. opening and closing of individual channels controls process

Inactivatedm similar to desensitization, channel no longer conducts ions even through it may appear open.

channel blocked by a component of the channel

Closed: all gates are closed

Closed (partially open): all but one gate is open

Open: all gates open, allowing ion flow

Inactivated: channel technically open but no longer conducting ion flow

summation of individual channels in different states produce macroscopic current, which is total current across membrane.

a. yes, you would need estimates for (1) tital # ion channels (2) open probability of those channels (3) equilbrium potential for ion

b. measure total current at given membrane potential

c. input membrane voltage, total current, & equilibrium potential into equation: I ion = G ion * (V m – E ion )

d. input total conductane, channel open probability (n^4) and # channels into following: G ion = n^4 (#channels)(g ion)(N^4 assumes K+ channel)

allwo precise measurements of ion channels opening and closing, gating properties, and conductance

VS voltage clamp measures average activity of Many channels and doesn’t provide single channel resolution of ion channel properties

enable diverse neuron types to have specialized signaling properties (ex: distinct firing patterns)

K+ channels are critical for generating resting membrane potential

S4 segment (contains positively charged amino acid residues)

Channel activation and inactivation kinetics: slower kinetics will lead to longer

action potential and lower frequency

b. For example, prolonged sodium channel inactivation will extend the refractory

period and decrease the maximum frequency of action potentials

Diverse channel types

Enables animals to receive quick feedback / respond quickly to sensory stimuli

b. Demyelination results in slowed or impaired conduction of action potentials

and can cause symptoms including motor deficits and muscle weakness (for

example in multiple sclerosis)

CNS myelination is achieved by oligodendrocytes and PNS myelination is achieved by Schwann cells

refers to the electrical potential difference across cell membrane when the cell is at rest (not actively recieving signals)

membrane permeability

concentration gradient of permeable ions across membrane

concentration gradient refers to the difference in ion concentration insdie the cell ([X] in) compared to outside ([X] out). this gradient drives the movemement of ions, creating an electrical difference

cell membrane’s selective permeability allows certain ions to move in or out based on their concentration gradients. This movement of ions results in a charge difference across membrane, creating resting membrane potential (Vrest)

increasing diameter increases speed of conduction with the square root of the diameter

relationship between diameter and speed of conduction is linear. meaning that as diameter increases, speed of conduction increases at a constant rate

optimal distance between nodes depends on the size of the(diameter) of axon. larger axons generally have greater internodal distances

schwann cell size limit lower end of internodal distances in peripheral axons. Schwann cells wrap around axon to form myelin sheath, their size sets minimum limit for the distance between nodes

myelination insulate the axon, whihc increases membrane resistance and decreases membrane capacitance, making electrical signal transmission more efficient

the action potential is generated. electrical signal spreads passively and very fast through myelinated section due to decreased capacitance.

The entire segment of the axon between the nodes is depolarized, allowing rapid signal transmission through the myelinated regions.

Schwann cells are responsible for myelinating axons in the peripheral nervous system (PNS).

Oligodendrocytes are responsible for myelinating axons in the central nervous system (CNS), and they can serve many axons with a single myelin layer.