39: Ion Channels and Pumps

physiological functions of ions:

• controls pace of the heart

• regulates secretion of hormones

• generates electrical impulses in the nervous system

ion channels:

pore forming plasma membrane proteins that open/close in response to chemical, temperature, or mechanical signals

Types of ion channels:

• resting ion channel

• voltage-gated ion channel

• ligand-gated ion channel

• signal-gated ion channel

resting ion channel:

always opened to generate resting membrane potentials, lets OUT ions

voltage-gated ion channels:

opens temporarily in response to change in membrane potential, lets IN ions

ligand-gated ion channels:

opens/closes in response to a specific extracellular neurotransmitter, lets IN ions

signal-gated ion channels:

opens/closes in response to a specific INTRAcellular molecule, lets IN ions

Na⁺/K⁺ across cell membrane:

• sodium ions IN always (diffusion)

• potassium ions OUT always (diffusion)

• exchange ions via ATPase pump

What are the 3 conformational states of a voltage-gated ion channel?

• closed: voltage sensor is in closed position, no ions in or out

• open: voltage sensor is in open position, ions move in

• inhibited: voltage sensor is open but a part of the protein is blocking the opening

voltage gated potassium channel:

• left quadrant assembles to form tetrameric structure

• each subunit has transmembrane region, cytoplasmic N and C terminus

• transmembrane region contains voltage sensor domain and pore forming domain

voltage gated sodium channel:

• four domains each w/ a S4 voltage sensing transmembrane helix

• can be modified by phosphorylation of an intracellular loop

• can be glycosylated in extracellular loop

voltage-gated calcium channels:

• 4 domains each w/ S4 voltage sensing domain and an activation gate at the pore

• direct block of the pore from extracellular side target regions within ion conducting pathway → obstructs permeation through the pore

leak channels:

slowly degrade the resting potential of neurons so cells actively transport ions to maintain a negative resting potential; energy independent

primed (resting) neurons have:

high concentrations of K+ on the inside and Na+ on the outside

When does depolarization of the plasma membrane occur?

when the voltage-gated sodium channels open (neuronal firing) → membrane potential becomes positive

What happens during repolarization?

K+ ions leave cell → decrease in membrane potential to negative value → voltage gated sodium channel closes

What happens during hyperpolarization?

delay in closing of the voltage gated potassium channels → overshoot of the resting membrane potential

What happens during the refractory period?

action potential can’t start again b/c sodium-potassium gradient hasn’t been restored by the exchange pump

Na+ ions:

• major extracellular cation

• responsible for osmotic pressure gradient between the interior of cells and their surrounding environment

K+ ions:

• major intracellular cation

• establishes resting membrane potential in neurons and muscle fibers

Cl- ions:

• primary extracellular anion

• contributes to osmotic pressure gradient

• important in maintaining proper hydration

Examples of natural toxins as channel blockers:

• chlorotoxin: Cl- channel blocker

• charybdotoxin: K+ channel blocker

• scyllatoxin: K+ channel blocker

• agitoxin: K+ channel blocker