nervous system 3

ion channels

specialised membrane proteins that select the type of ion (or ions) that they allow to pass through the membrane.

types of ion channels

leak channels and gated ion channels

leakage channels: always open

• called leakage channels due to them being consistently open.

• said to open and close randomly, they can essentially be treated as permanently open.

• enable ions to leak into or out of the cell, aligning with their concentration gradient.

gated ion channels

change conformation/shape and open/close in response to specific signals or stimuli.

gated ion channels: ligand-gated ion channels

• respond to chemical signals or ligands that bind to them

• once bound, triggers the opening of the ion channel, permitting ions to flow into or out of the cell and hence, altering the cells permeability to that particular ion.

• abundant in chemical synapses with neurotransmitters acting as ligands to initiate ion channel opening.

gated ion channels: mechanically gated ion channels.

• prevalent in sensory receptors, especially those associated with touch in the skin.

• mechanical stimuli activate these channels

• ion channel opens upon mechanical stimulation, allowing ions to move in or out of the cell according to their concentration gradients.

gated ion channels: voltage-gated ion channels

• sensitive to changes in membrane voltage

• in excitable cells (e.g. neurons and muscles) there is a difference in eletrical charge across the cell membrane

• voltage channels can trigger the opening of voltage gated ion channels.

• these channels play a pivotal role in generating and propagating action potentials in neurons and excitable cells.

• found along neuron exons and plasma membrane of muscle cells.

resting membrane potential

nerve and muscle cells can change their potential in a precise, regulated way.

• forms the basis of how nerve cells communicate with one another.

• transient changes in the membrane potential from its resting level produce electrical signals.

graded potentials

signal over short distances

action potentials

signal over long distances

• to get an electrical signal to start, the membrane potential has to change

steps of action potentials

1. membrane potential stays at resting voltage until something changes

2. channels that start depolarizing the membrane because of a stimulus help the cell depolarise from -70mV to -55mV

3. once the membrane reaches -55mV, voltage gated Na+ channels open and an action potential starts

4. voltage-gated channels open in response to changes in charge distributed across the membrane during repolarisation

5. K+ ions leave the cell

6. hyperpolarization

resting state

At the resting state, the cell's membrane potential is -70 millivolts. Ion movement primarily occurs through leak channels and sodium-potassium pumps. All voltage-gated channels, including sodium and potassium, remain closed. This state sets the baseline for the subsequent action potential process.

stimulus depolarises membrane to threshold

Graded potentials are initiated by external stimuli and reach the axon hillock. These graded potentials cause depolarisation of the membrane at the axon hillock, pushing it closer to the threshold value. The axon hillock accumulates these graded potentials, and their summation can elevate the membrane potential to -55 millivolts, known as the threshold potential.

depolarisation phase

Upon reaching the threshold potential of -55 millivolts, voltage-gated sodium channels rapidly open. Sodium ions rush into the cell due to the higher concentration outside. The influx of positively charged sodium ions leads to significant depolarisation. This rapid depolarisation phase sees the membrane potential increase from -55 millivolts to approximately +30 millivolts.

repolarisation phase

As the membrane potential reaches its peak positive value, inactivation gates of voltage-gated sodium channels close. Simultaneously, voltage-gated potassium channels start opening. These channels, though slower to open, permit potassium ions to exit the cell. The efflux of positively charged potassium ions initiates repolarisation, causing the membrane potential to become more negative.

hyperpolarisation phase

Voltage-gated potassium channels continue to remain open, allowing more potassium ions to leave the cell. As a result, the cell loses a positive charge, making the internal environment more negative than the resting potential. This brief hyperpolarisation phase showcases the membrane potential dropping below the resting value of -70 millivolts.

return to resting state

Even as the membrane potential returns to -70 millivolts, some voltage-gated potassium channels remain open. This ongoing outflow of potassium ions leads to a more negative membrane potential than the resting state. However, these voltage-gated potassium channels eventually close, leaving only leak channels and the sodium-potassium pumps to maintain ion balance. Regardless of the starting point, when only leak channels and pumps are active, the membrane potential returns to the resting value of -70 millivolts. This sequence marks the completion of the action potential process.

chemical synapses

• neurotransmitter is released from one cell and it affects the other cell

• involve the transmission of chemical information from one cell to the next

• transmits signals (action potentials) between neurons or neurons and muscles or glands

neurotransmitter

chemical signal that is released from the synaptic end bulb of a neiron to cause a change in the target cell

chemical synapse

connection between two neurons, or bewteen a neuron and its target, where a neurotransmitter diffuses across a very short distance.

synaptic cleft

small gap between cells in a chemical synapse where neurotransmitter diffuses from the presynaptic element to the postsynaptic element.

steps of neurotransmission

1. the action potential travels down the axon to the axon terminal, one of the branches at the very end of the axon.

2. the electrical signal causes the axon terminal to release the neurotransmitter it has stored.

3. neurotransmitter travels across the space between the two neurons (synaptic cleft)

4. neurotransmitter binds to receptors on the postsynaptic membrane, and binding triggers a change in the cell

impact of drugs, neurotoxins and diseases can be grouped by…

• Where they act

- CNS, PNS, neuromuscular junction

- Ion channels, receptors, enzymes, synapses

• What they do (excite, inhibit, block, mimic, disrupt)

• Which neurotransmitter system they influence

• Their clinical/behavioural effect

• Their mechanism of action

mechanism of action: nervous system functioning can be altered by affecting…

1. ion channels

2. neurotransmitter release

3. neurotransmitter binding to postsynaptic receptors

4. neurotransmitter degradation (preventing removal of neurotransmitter)

ion channels

blocking or disrupting various ion channels to disrupt normal functioning

• Na+ channels

• K+ channels

• Ca2+ channels

• Cl- channels

e.g. numerous toxins from animal venoms (snake, spider)

neurotransmitter release: inhibiting

• botulinum toxin (botox)

• tetanus toxin

neurotransmitter release: increasing

red back spider venom

receptor binding: activating receptors (‘mimicking neurotransmitter’)

• nicotine

• opioids (e.g. morphine, heroin)

• benzodiazepines (e.g. valium)

receptor binding: blocking receptors (antagonists)

• some venom/toxins

• curare

• ketamine

• caffeine

preventing neurotransmitter removal: preventing re-uptake

• cocaine

• SSRI’s (antidepressants)

preventing neurotransmitter removal: preventing breakdown

• organophosphate insecticides

• nerve agents