Nerve Impulses and Synaptic Transmission

2 principal parts of Nervous system

• Central nervous System(CNS)

• Peripheral Nervous System (PNS)

• Walls of GI tract also contain neurons called the enteric nervous system

CNS

• Brain and spinal cord of dorsal cavity

• Integration + control center

  • interprets sensory input and dictates motor output

PNS

• The portion of nervous system outside of CNS

• Consists mainly of nerves and extend from brain and spinal cord

  • Spinal nerves to and from spinal cord

  • Cranial nerves to and from the brain

Nervous System

2 functional divisions of PNS

• Sensory

• Motor

Sensory(afferent) division

• Somatic sensory fibers: convey impulses from skin, skeletal muscles, and joints to CNS

• Visceral sensory fibers: convey impulses from visceral organs to CNS

Motor (efferent) division

• Transmits impulses from CNS to effectors

  • Muscles and glands

• Two divisions

  • Somatic nervous system

  • Autonomic nervous system

2 principal cell types of Nervous tissue

• Neuroglia (glial cells): small cells that surround and wrap delicate neurons

• Neurons (nerve cells): excitable cells that transmit electrical signals

4 main neuroglial cells that support CNS neurons

1. astrocytes

2. Microglial cells

3. Ependymal cells

4. oligodendrocytes

Astrocytes

• Most abundant, versatile, and highly branched of glial cells

• Cling to neurons, synaptic endings, and capillaries

6 functions of neuroglia

• Support and brace neurons

• Play role in exchanges between capillaries and neurons

• Guide migration of young neurons

• Control chemical environment around neurons

• Respond to nerve impulses and neurotransmitters

• Participate in information processing in brain

Microglia

• mall, ovoid cells with thorny processes that touch and monitor neurons

• Migrate toward injured neurons

• Can transform to phagocytize microorganisms and neuronal debris

Ependymal cells

• Range in shape from squamous to columnar

• May be ciliated

• Cilia beat to circulate CSF

• Line the central cavities of the brain and spinal column

• Form permeable barrier between cerebrospinal fluid (CSF) in cavities and tissue fluid bathing CNS cells

Oligodendrocytes

• Branched cells

• Processes wrap CNS nerve fibers, forming insulating myelin sheaths in thicker nerve fibers

2 neuroglia of PNS

• Satellite cells

• Schwann cells

Satellite cells

• Surround neuron cell bodies in PNS

• Function similar to astrocytes of CNS

Schwann cells

• Surround all peripheral nerve fibers and form myelin sheaths in thicker nerve fibers

  • Similar function as oligodendrocytes

• Vital to regeneration of damaged peripheral nerve fibers

Neurons

• (nerve cells) are structural units of nervous system

• Large, highly specialized cells that conduct impulses

• All have cell body and one or more processes

Special characteristics of neurons

• Extreme longevity (lasts a person’s lifetime)

• Amitotic, with few exceptions

• High metabolic rate: requires continuous supply of oxygen and glucose

Resting membrane potential

• ~-70 mV for neurons

• It is the potential that is generated when neurons are at rest

Membranes of neurons

• Hydrophilic head+ hydrophobic tails

• arranged in a bilayer

Will either water molecules or ions cross the plasma membrane

No because the hydrophobic area DOES NOT allow charged ions to go freely from one side to the either

Solution: Channels

Chemically gated channels

• also known as ligand-gated channels,

• open when the appropriate chemical (in this case a neurotransmitter) binds

Voltage gated ion channels

open and close in response to changes in the membrane potential

Ions in ECS vs ICS during resting membrane potential

• The cell cytosol contains a lower concentration of Na+ and a higher concentration of K+ than the extracellular fluid.

• Negatively charged (anionic) proteins balance K+

• Na+ and other cations are balanced chiefly by chloride ions .

in both fluids, K+ plays the most important role in generating the membrane potential.

What will K+ do if there were ONLY K+ channels

• It will diffuse down its concentration gradient and cross the channel from intracellular to extracellular

• results in a negative membrane potential= higher electrical gradient

• electrical gradient will pull K+ from extra- to intra

• At -90 mV, the concentration+ electrical gradients for K+ are balanced

What would happen if N+ channels were added alongside K+ channels

• Na+ entry via a FEW leakage channels reduces the negative membrane slightly to -70 mV

What would happen if Na+/K+ ATPase was channels alongside the K+ and Na+ channels

• It will maintain the concentration gradient and maintain the resting membrane potential

• It transports any extra K+ in and Na+ out that leak through the channels

  • prevents the membrane from having equal concentration of both ions

Generating a resting membrane potential depneds on 2 differences

1. differences in K+ and Na+ concentrations inside and outside cells

2. differences in permeability of the plasma to these ions

Plasma membrane permeability

• At rest= impermeable to anionic proteins

• slightly permeable to Na+

• 25x MORE permeable to K+ than Na+

  • since K+ diffuses out of cell down its concentration gradient much easier

• quite permeable to Cl-

Graded potentials

• are short-lived, localized changes in membrane potential

• usually in dendrites or the cell body.

• They can either be depolarizations or hyperpolarization’s

• Purpose: sum together to determine whether or not AP will occur

Why are graded potentials ‘graded’

• because their magnitude varies directly with stimulus strength.

• The stronger the stimulus, the more the voltage changes and the farther the voltage change extends.

• weaker stimulus= decay and less spread of voltage change

  • due to voltage being lost via leaky channels

3 Types of graded potentials

• receptor potential/generator potential

• postsynaptic potential

  • is produced when the stimulus is a neurotransmitter released by another neuron.

  • The neurotransmitter is released into a fluid-filled gap called a synapse and influences the neuron beyond the synapse.

• end-plate potential

Action potentials

• Brief reversal of membrane potential with a change in voltage of ~100 mV (from -70 to +30 mV) in a patch of membrane depolarized by local currents

• principal way neurons send signals means of long-distance neural communication

• do not decay in amplitude with distance traveled as graded potentials do

• occur only in cells with excitable membranes (neurons & muscle cells)

• in neurons

  • only axons can generate action potentials

  • also referred to as a nerve impulse

  • Voltage-gated channels on axons open in response to local currents (graded potentials)

K+ channel

Has an activation gate can either be opened or closed

Na+ channel

• Has 2 gates

• Both must be open for AP to continue

• Gate A opens and Gate B closes during AP

  • No more flow of ions

  • Gate and Gate B alternate closing, which takes time

Action Potential steps

1. Resting states

2. Depolarization

   • Has a rising phase

3. Repolarization

   • Overshoot

   • Falling phase

4. Hyperpolarization

   • Refractory period

   • Return to rest

Resting state

• ALL voltage-gated Na+ and K+ channels are closed.

• Only the leakage channels are open, maintaining resting membrane potential.

• Each Na+ channel has two gates:

  • a voltage-sensitive activation gate that is closed at rest and responds to depolarization by opening,

  • an inactivation gate that blocks the channel once it is open.

• depolarization opens and then inactivates sodium channels.

What must occur for Na+ to enter the cell

• Both gates must be open for Na+ to enter,

• BUT the closing of either gate effectively closes the channel.

• In contrast, each voltage-gated K+ channel has a single voltage-sensitive gate that is closed in the resting state and opens slowly in response to depolarization.

Depolarization

• Voltage-gated Na+ channels open.

• influx of positive charge(Na+ ions) depolarizes that local patch of membrane further, opening more Na+ channels so the cell interior becomes progressively less negative

• When threshold of (-55 and -50 mV), depol. becomes self-generating until ALL Na+ channels are open

  • permeability of Na+ is 1000x greater than in a resting neuron

• eventually membrane potential reaches +30 mV

Rising phase

• Rapid opening of all Na+ channels

• Occurs only if certain threshold is met or else AP will not be generated

Repolarization

Na+ channels are inactivating, and voltage-gated K+ channels open

• Inactivation gates of Na+ begin to close

• Na+ permeability declines to resting levels and influx of Na+ eventually stops and AP stops rising

• Slow voltage-gated K+ channels open and K+ rushes OUT of cell

  • restores the negativity of the resting neuron

Both the abrupt decline in Na+ permeability and the increased permeability to K+ contribute to repolarization

Hyperpolarization

• Some K+ channels remain open, and Na+ channels reset.

• The period of increased K+ permeability typically lasts longer than needed to restore the resting state.

• As a result of the excessive K+ efflux before the potassium channels close(hyperpolarization) is

  • AKA a slight dip following the spike.

• At the end of this phase, the Na+ channels have reset to their original position by changing shape to reopen their inactivation gates and close their activation gates.

Falling phase

Na+ channels stay inactivated

Opening of all K+ channels

Vm repolarizes

inactivation gate opens and Na+ closes

2 types of synapses

1. Chemical synapse

2. Electrical synapse

Chemical synapses

Most common type

specialized for the release and binding of neurotransmitters

Separated by synaptic cleft (fluid-filled space of 30-50 nm)

2 parts that make up chemical synapses

• Axon terminal of presynaptic neuron: contains synaptic vesicles filled with neurotransmitter

• Receptor region on postsynaptic neuron’s membrane: receives neurotransmitter

  • Usually on dendrite or cell body

6 Steps of Information transfer across chemical synapses

1. AP arrives at axon terminal

2. Voltage-gated Ca2+ channels OPEN and Ca2+ enters axon terminal

3. Ca2+ entry causes synaptic vesicles to release neurotransmitters by EXOcytosis

4. Neurotransmitter diffuses across synaptic cleft and binds to specific receptors on the postsynaptic membrane

5. Binding of neurotransmitter opens ion channels, resulting in graded potentials

6. Neurotransmitters effects are terminated

How are neurotransmitter effects terminated

1. Reuptake by astrocytes or the presynaptic terminal, where the neurotransmitter is stored/destroyed by enzymes(i.e. norepinephrine)

2. Degradation by enzymes associated with postsynaptic membrane or present in the synaptic cleft (i.e. Ach)

3. Diffusion away from the synapse

Postsynaptic potentials

Neurotransmitter receptors cause graded potentials that vary in strength

based on:

• Amount of neurotransmitter released

• Time neurotransmitter stays in cleft

• Depending on effect of chemical synapse, there are two types of

postsynaptic potentials

• EPSP: excitatory postsynaptic potentials

• IPSP: inhibitory postsynaptic potentials

What is the effect of neurotransmitters

Excitatory

Inhibitory

To determine if neurotransmitters either of this,

• Depends on neurotransmitter and its receptors

Ionotropic receptors

• AKA channel linked receptors are ligand-gated ion channels that mediate DIRECT neurotransmitter action

• As ligand binds to 1 or more receptor subunits, proteins change shape

  • this opens central channel and allows ions to pass

  • Rapid synaptic transmission

• ALWAYS located on opposite of site of neurotransmitter release

• At excitatory receptor sites (ie.e receptors for Ach, glutamate, aspartate, ATP), the ionotropic receptors are cation channels(Na+, K+, Ca2+), where Na+ entry contributes the MOST to depolarization

  • Sensitive to molecules and sometimes, membrane potential

  • Selective for specific ions

• Respond to GABA and glycine

• Allows Cl- to pass

• mediates hyperpolarization

Metabotropic receptors

aka G Protein-coupled receptors

Responses are indirect, complex, slow, and often prolonged

G-protein activates second messenger system

Involves transmembrane protein complexes

Cause widespread metabolic changes, which is why they are termed G protein-coupled receptors

Examples of metabotropic receptors

• Biogenic amine receptors

• neuropeptide receptors

• Muscarinic ACh receptors

WHat happens when neurotransmitters bind to a G-protein-coupled receptor

The G-protein is activated

Activated G proteins typically work by increasing or decreasing the amount of second messengers like cyclic AMP, cyclic GMP, diacylglycerol, or Ca2+ in the cytoplasm

G protein-coupled receptors cause the formation of 2nd messengers

Neurotransmitters

along with electrical signals, are the

language of nervous system

• 50 or more neurotransmitters have been identified

• Classified chemically and functionally

Glutamatergic receptors

• Glutamate=Most abundant excitatory neurotransmitter in the brain

• Can activate ionotropic and metabotropic receptors

Excitatory synapses and EPSPs

• Neurotransmitter binding opens chemically gated channels on POSTsynaptic membranes

• Each channel allows simultaneous diffusion of Na+ and K+ into membrane but in opposite directions

• Na+ influx greater than K+ efflux, resulting in local net graded potential depolarization called excitatory postsynaptic potential (EPSP) NOT an AP

  • because APs don’t occur in membrane that have ONLY chemically-gated channels

  • postsynaptic membranes do not generate APs

• EPSPs trigger AP if EPSP is of threshold strength to depolarize axon

  • Can spread to axon hillock and trigger opening of voltage-gated channels, causing AP to be generated

Excitatory postsynaptic potentials (EPSPs)

• Is what is generated by chemically-gated channels of postsynaptic membranes

GABAergic receptors

GABA is responsable for most inhibitory transmission

• GABARs bind ethanol, benzodiazepine, barbiturate

Inhibitory Synapses and IPSPs

• Binding of neurotransmitter reduces postsynaptic neuron’s ability to generate an AP

• Neurotransmitter binding to receptor opens chemically gated channels that allow entrance/exit of ions that cause hyperpolarization

• Makes postsynaptic membrane more permeable to K+ or Cl–

  • If K+ channels open, it moves out of cell

  • If Cl– channels open, it moves into cell

• Moves neuron farther away from threshold (makes it more negative)

Inhibitory postsynaptic potentials (IPSPs)

are hyperpolarizing changes in potential

ACh receptors

• 2 subtypes of cholinergic receptors

  • Nicotinergic

  • Muscarinic

• Each subtype has a different antagonists (curare and atropine)

Norpepinephrine receptors

Summary of neurotransmitters

Summation by postsynaptic neuron

• A single EPSP cannot induce an AP, but EPSPs can summate (add together) to influence postsynaptic neuron

• IPSPs can also summate

• Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons

• Only if EPSPs predominate and bring to threshold will an AP be generated

Where do excitatory synapses often occur

on dendrites

Where do inhibitory synapses often occur

often on the cell body

2 types of summations

1. Temporal

2. Spatial

Temporal summation

One or more presynaptic neurons transmit impulses in rapid-fire order

• First impulse produces EPSP, and before it can dissipate another EPSP is

triggered, adding on top of first impulse

Spatial summation

Postsynaptic neuron is stimulated by large number of terminals simultaneously

• Many receptors are activated, each producing EPSPs, which can then add together