21. Drug Action on Ion Channels and Pumps

Question 1

Identify the 4 physiological functions of ions.

Answer 1

1. control the pace of the heart
2. regulate the secretion of hormones
3. generate electrical impulses in the nervous system
4. dysfunctions in the ions are linked to physiological, neuronal, and other disorders

Question 2

What is the physiological function of Na+?

Answer 2

Na+ is the major extracellular cation
* responsible for osmotic pressure gradient between the interior of cells and their surrounding environment

Question 3

What is the physiological function of K+?

Answer 3

The major intracellular cation
* establishes the resting membrane potential in neurons and muscle fibers

Question 4

What is the physiological function of Cl-?

Answer 4

Cl- is the predominant extracellular anion
* contributes to osmotic gradient
* important for maintaining proper hydration

Question 5

Uptake of Na+ ions via Na+ channels by ____.

Answer 5

diffusion

Question 6

Efflux K+ ions via K+ channels by ___.

Answer 6

diffusion

Question 7

Exchange Na+-K+ ions by ___.

Answer 7

an ATPase-dependent pump

Question 8

Describe what resting potential is.

Answer 8

Resting potential is the stable membrane potential in a resting cell.

Question 9

Explain what an action potential is.

Answer 9

Action potential is a short event, in which membrane potential rises and falls.

Question 10

Describe the cycle of resting and action potentials.

Answer 10

1. Stimulus causes rapid change in voltage or action potential.
2. Depolarization caused by a rapid rise in membrane potential from opening of Na+ channels.
3. Membrane repolarization from rapid Na+ channel inactivation and efflux of K+ ions from activated K+ channels.
4. Hyperpolarization with a lowered membrane potential caused by the efflux of K+ and closing of the K+ channels.
5. Return to resting voltage.

Question 11

Describe the characteristics of ion channels.

Answer 11

Ion channels are pore-forming plasma membrane proteins that can open/close in reponse to chemical, temperature, or mechanical signals.
* an open channel allows specific ions to rapidly traverse the transmembrane along an electrochemical gradient –> generates electrical signal that is propagated along excitable cells.

Question 12

Describe resting ion channels.

Answer 12

Efflux ion by the always opened ion channel to generate resting membrane potential.

Question 13

Describe ligand-gated ion channels.

Answer 13

Uptake ion by opening the channel in response to a specific extracellular ligand
* contains two ligand binding sites
* activation by a ligand triggers a conformational change that opens the gate
* ex. neurotransmitter

Question 14

Describe voltage-gated channels.

Answer 14

Uptake ion by opening the channel in response to changes of the membrane potential.
* contains a “voltage sensor”
* contains a transmembrane helix that changes orientation depending upon membrane polarization.
* 4 domains (each with a S4 voltage sensing transmembrane helix (VSD) and activation gate of the pore domain (VD))
* can be directly blocked by pore blockers on the extracellular side of the pore.

Question 15

Describe the three conformational states of a voltage-gated ion channel.

Answer 15

• closed state - the voltage sensor is in the closed orientation
• open state - the voltage sensor is in the open orientation
• inhibited state - the coltage sensor is in the open orientation, but a part of the protein blocks the opening

Question 16

Describe signal-gated channels.

Answer 16

Uptake ion by opening the channel in response to an intracellular molecule.
* ex. G-protein, cyclic GMP,

Question 17

What are the effects of toxins from deathstalker scorpions?

Answer 17

Deathstalker scorpions are ion channel blockers

Contain 4 key toxins:
* chlorotoxin: Cl-channel blocker
* charybdotoxin: K+ channel blocker
* scyllatoxin: K+ channel blocker
* agitoxin: K+ channel blocker