ZIMA Lecture 3: Channel Structure and Function

Question 1

Ion channels are transporters that use _________

Ion channels have ________ pores that can open and close ______

Ion selectivity (selective filter) means ______

Ion channels are/are not continously open. They are ____ between open and closed states. With prolonged stimulation, most channels_____

Answer 1

Ion channels are transporters that use electrochemical potential

Ion channels have narrow, highly selective pores that can open and close rapidly

Ion selectivity (selective filter) means permitting to pass specific ions (Na or K or Ca or Cl)

Ion channels are NOT continously open. Instead, they are gated between open and closed states. Moreover, with prolonged stimulation, most channels go into a closed “inactivated” state

Question 2

What are the three major types of ion channels?

Answer 2

Channel gating is controlled either by:
1. voltage

2. ligand
3. mechanical stress

Question 3

At rest, the cell membrane is freely permeable to which ion?

What creates the negative membrane potential?

When does the net effux of that ion stop?

What does ‘Nernst potential’ for that ion mean?

Answer 3

At rest the cell is freely permeable to K+

K+ leak from the cell creates a negative membrane potential

The net efflux of K+ halts when the membrane potential reaches a value at which electrical driving force on K+ exactly balance the effect of its concentration gradient.

K+ equilibrium potential (K Nernst potential): the membrane potential at which there is no net flux of K+

Question 4

What are the three things that determine Nernst Potential?

What are the two equations for Nernst Potential?

Answer 4

Nernst potential is determined by:

1. Ion concentrations
2. Temperature
3. Ion valence

Note: only a very small numner of ions must move across the membrane to set up membrane potential. It takes just 10^-12 M of potassium per square centimeter to develop membrane potential of -100 mV

Question 5

Explain the role of K leak vs Na/K ATPase pump in the development of the resting membrane potential

Answer 5

Because the Na/K pump is electrogenic, it can also contribute to the RMP. However, this contribution is significantly smaller (around 10%) compared to K+ leak channels (90%)

Question 6

Explain the structure of ion channels:

Answer 6

Negative charged amino acids concentrated at the cytosolic entrance of the pore attract cations and repel anions, making the channel cation-selective

K+ ions must lose all of its bound water to enter filter

The channel gating (a transition between closed and open state) involved the movement of the helices in the membrane so they either obstruct (the closed state) or free (open state) the path for ions

Question 7

What are the three voltage gated cation channels?

What are the three excitatory transmitter gated ion channels?

What are the two inhibitory transmitter gated ion channels?

Answer 7

Voltage gated cation channels: voltage gated Na channels, voltage gated K channels, voltage gated Ca channels

Excitatory: ACh gated cation channels, Glutamate gated Ca channels, serotonin gated cation channel

Inhibitory: GABA gated Cl- channels, Glycine gated Cl- channels

Question 8

The main task of neurons is to ____, ____, _____

The signal is always the same: ______

How can neurons communicated with each other?

Answer 8

The main task of nerusons is to receive, conduct, and transmit signals.

The signal is always the same: the action potential

By changing firing a frequency of action potentials, neurons communicate with each other

Question 9

Na+ channels are activated by?

Na+ channel activation increases w/______

The positive feedback is counterbalanced by what two things?

Answer 9

Na+ channels are activated by membrane depolarization

Na+ channel activation increases with depolarization (positive feedback)

The positive feedback is counterbalanced by 1) Na+ channel inactivation and 2) opening voltage-activated K+ channels

Question 10

Explain the ball and chain model of inactivation

Answer 10

Question 11

What is responsible fo action potential propogation?

Answer 11

Na+ channel inactivation is responsible for unidirectional propogation of the action potential (when AP has reached the axon terminal it will not go back to the soma)

Question 12

What happens if you induce an AP in the middle?

Answer 12

The AP will carry on in both directions

Question 13

What are the two major components of total membrane current?

What does membrane depolarization lead to?

Answer 13

Total membrane current has two major components:

1. Initial Inward Current (Na+)
2. Late Outward Current (K+)

Membrane depolarization leads to:

1. Activation of Na+ channels
2. Subsequent Inactivation of Na+ channels
3. Activation of K+ channels (with a delay)

Question 14

Explain the myelination of neurons

Answer 14

The axons of many vertebrate neurons are insulated by myelin sheath, which GREATLY INCREASES the rate at which an axon can conduct an AP.

Myelin produced by Schwann Cells (PNS)

Oligodendrocytes (CNS)

Myelin sheath interrupted at nodes of Ranvier (where the sodium channels are concentrated)

AP propogates along an axon quickly by jumping from node to node (saltatory conduction)

Question 15

Explain the patch-clamp technique.

Answer 15

Whole cell currnet is the summation of all single channel currnets in the cell membrane.

The patch clamp technique allows studying ion current through a single molecule of a channel protein.

All single channels open in an all or nothing fashion

Question 16

Neuronal signals are transmitted from cell to cell at specialized sites known as _____.

Transmission of signals is usually indirect: it involves what two things?

Answer 16

Neuronal signals are transmitted from cell to cell at specialized sites known as synpases.

Transmission of signals is usually indirect.

It involves 1) neurotransmitter and 2) transmitter-gated ion channels

Question 17

Explain transmitter gated ion channels

Answer 17

Transmitter gated ion channels open transiently in reponse to the binding of neurotransmitters, thereby producting a brief increase in ion conductance.

Transmitter gated ion channels produce local changes of membrane potential, that are graded according to the amount of neurotransmitters and how long it persists at the synpases

Question 18

Excitatory vs Inhibitory NTs

Answer 18

Excitatory NTs depolarize the post-synaptic neuron (open Na+ channels)

Inhibitory NTs hyperpolarize the post-synaptic neuron (open K+ of Cl- channels)

Question 19

Explain the ACh receptor

Answer 19

The ACh receptor (nicotonic) is opened upon the release of ACh from the nerve terminal at the neuromuscular junction (activation of skeletal muscle contraction)

Two binding sites for ACh

This was the first ion channel to be cloned, sequences, and characterized in terms of single channel properties

Question 20

Explain the cascade of events at the Neuromuscular Junction

Answer 20

1. Opening of voltage gated Ca++ channels in the nerve terminal membrane causes a release of ACh into the synaptic cleft
2. Activation of ACh receptors in the muscle cell causes a local membrane depolarization
3. Activation of voltage gated Na+ channels causes the action potential generation
4. Membrane depolarization activates voltage gated Ca++ chjannels in the T-tubules
5. This causes Ca release from the sarcoplasmic reticulum and muscle contraction

Question 21

RMP of the nerve cell is a direct consequence of:

Answer 21

High K+ channel permeability/ K+ leak

Question 22

Which agent could paralyze/stop skeletal muscle activity?

Answer 22

Nicotinic Receptor Blocking Agent

REMEMBER: Nicotinic is skeletal

Muscarinic is smooth