Lecture 3 - Graded Potentials, Action Potentials and Synapses

Types of Gated Ion Channels

• Chemically gated (ligand-gated) channels

• Voltage-gated channels

• Mechanically gated channels

Chemically gated (ligand-gated) channels

Open only with binding of a specific chemical (example: neurotransmitter)

Voltage-gated channels

Open and close in response to changes in membrane potential

Mechanically gated channels

Open and close in response to physical deformation of the membrane, as in sensory receptors

When gated channels open, ions diffuse quickly along

• The chemical concentration gradients from higher concentration to lower concentration

• Along electrical gradients toward opposite electrical charge

Changes in Membrane Potential occurs when

(1) Ion concentrations change

(2) permeability to ions (channel opening) changes

Depolarization

• Decreased membrane potential (toward zero)

  • Inside membrane less negative

  • AP probability increases

Hyperpolarization

• Increase in membrane potential (further from zero)

  • Inside of membrane more negative

  • AP probability decreases

Graded Potentials

• Short-lived, local (short distance signals

• Stronger stimulus → increased magnitude

• Spreads but current decays with distance, time (decremental)

• Depolarizing or hyperpolarizing

Receptor potential

receptors of sensory neurons

Postsynaptic potential graded potential

dendrite or soma of neuron or muscle cell

Action Potentials

• Principal means of long-distance neural communication

• Only occur in muscle cells and axons of neurons (excitable cells)

• Involves opening of specific voltage-gated channels

• Brief reversal of membrane potential with a change in voltage of ~100 mV

• Do not decay with distance

Voltage-gated Na+ and K+ channels give neurons ability to ____________

Generate and propagate action potentials

Action potential Mechanism

1. Steady resting membrane potential is near EK, PK>PNa, due to leak Kt channels.

2. Local membrane is brought to threshold voltage by a depolarizing stimulus.

3. Current through opening voltage-gated Na+ channels rapidly depolarizes the membrane, causing more Na* channels to open.

4. Inactivation of Nat channels and delayed opening of voltage-gated Kt channels halts membrane depolarization.

5. Outward current through open voltage-gated K* channels repolarizes the membrane back to a negative potential.

6. Persistent current through slowly closing voltage-gated K* channels hyperpolarizes membrane toward Ek; Na* channels return from inactivated state to closed state(without opening).

7. Closure of voltage-gated K* channels returns the membrane potential to its resting value.

Absolute refractory period

The brief interval following an action potential during which a neuron is completely unable to fire a second action potential, regardless of the stimulus strength

Relative refractory period

The phase following the absolute refractory period during which a neuron can fire a second action potential, but only in response to a stronger-than-normal stimulus

Threshold Potential

• Depolarization triggers an AP only when the membrane potential exceeds a threshold potential (~-55 mV) .

• Regardless of the size of the initial stimulus, if the membrane reaches threshold, the APs generated are all the same size and do not decay.

• A single AP cannot convey information about the magnitude of the initial stimulus

Action Potential Thresholds

• An action potential is an all-or-none event generated by a positive- feedback loop.

• The threshold indicates whether or not incoming stimuli are sufficient to generate an action potential (i.e. whether the feedback loop will work).

• The value of threshold can vary according to numerous factors.

• Changes in the ion conductances of sodium or potassium, or the availability of voltage-gated Na+ channels, can lead to a raised or lowered value of threshold

Action Potential Propagation

• Current entering during an AP is sufficient to easily depolarize adjacent membrane to the threshold potential.

• Propagation of AP from the initial segment to the axon terminal is typically one-way because the absolute refractory period follows along in the “wake” of the moving AP

Action Potential Conduction Speed

• Depends on fiber diameter and whether the fiber is myelinated.

• Larger caliber axons allow current to flow more easily, speeding up propagation

Saltatory Conduction

The process where action potentials "jump" from one node of Ranvier to the next along a myelinated axon, significantly increasing the speed of nerve impulse transmission compared to unmyelinated axons

Graded Potentials vs Action Potentials

Synapse

Point of communication between two neurons (or neuron and muscle cell)

Chemical synapse

Neurotransmitters relay information from pre- to postsynaptic cell across synaptic cleft

Electrical synapse

• pre- and post- synaptic cells joined by gap junctions

• in CNS

Mechanism of Neurotransmitter Release

• Neurotransmitter stored in vesicles

• Vesicles docked on PM at release regions known as active zones

• Transmitter release initiated when AP reaches synaptic bouton

• The AP depolarizes the membrane in bouton causing voltage-gated Ca2+ channels to open.

• Ca2+ activates vesicle docking and fusion with the PM

1. Action. potential reaches terminal

2. Voltage-gates Ca2+ channels open

3. Calcium enters axon terminal

4. Neurotransmitter release and diffusion

5. Neurotransmitter binds to postsynaptic receptors

6. Neurotransmitter removed from synaptic cleft

Activation of the Postsynaptic Cell

• NT diffuses across synaptic cleft (0.2 msec delay) and binds to postsynaptic receptors.

• Ionotropic receptors – ligand-gated ion channels

• Metabotropic receptors – mediate slower actions through G-protein second messengers

Excitatory Chemical Synapses

• Glutamate

• iGluRs: non-selective cation channels

• EPSP: membrane potential closer to threshold

• Changes in synaptic strength underlie learning and memory

Dendritic Spines

• Protrude from the main shaft of dendrite, single synapse at head.

• Heterogeneous in size, shape

• Modified by activity and experience

• Morphological basis for synaptic plasticity

• Receptors, signaling proteins clustered in PSD

Inhibitory Chemical Synapses

• GABA and glycine

• Hyperpolarization caused by:

  • Opening Cl- channels in neurons where ECl < Er

  • Increased K+ permeability moves membrane potential towards EK (-90 mV)

IPSP causes what?

hyperpolarization (membrane potential further from threshold)

Synaptic Integration

• Neurons undergo many EPSPs (A) and IPSPs (B)

• Receive excitatory and inhibitory input

Axon Initial Segment

• Lower threshold than axon for AP generation due to high VGSC concentration

• Sensitive to small changes in the membrane potential that occur in response to synaptic potentials on soma and dendrites.

• Location of individual synapses on the postsynaptic cell is important

Presynaptic modulation of synaptic strength

• ↑ [Ca2+i] during high frequency stimulation → increases NT release

• Axo-axonic input (facilitation or inhibition)

• Auto-receptors: -ve feedback decreases NT release

Postsynaptic

• Paired-pulse facilitation

• Desensitization – receptor responds then fails despite continued presence of NT (receptor internalization).

Drug effects on synaptic effectiveness

• Release and degradation of the NT inside the axon terminal.

• ↑ NT release into the synapse.

• ↓ NT release into the synapse.

• Inhibition of synthesis of the NT.

• ↓ reuptake of the NT from the synapse (e.g. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that affect serotonin levels in the brain)

• ↓ degradation of the NT in the synapse.

• Agonists (evoke same response as neurotransmitter) or antagonists (block response to neurotransmitter) can occupy the receptors.

• ↓ biochemical response inside the dendrite

Subthreshold stimulus

doesn’t cause reaction

Threshold stimulus

Cause reaction

Single AP doesn’t tell us anything about _____

Strength of stimulus

Increase amplitude of stimulus=

Increased frequency of AP

Ionotropic receptors

Directly control ion channels and produce fast, brief responses

Metabotropic receptors

Use G proteins and second messengers for slower, more widespread, and long-lasting cellular effects