Physiology - Reflexes

PHYSIOLOGY: REFLEXES Page 1

REFLEXES

Definition of Reflex – a stereotyped response to specific

stimulus; any response that occur automatically without

conscious effort

Two types of Reflex

a. Simple or Basic Reflex – built-in, unlearned

responses, e.g., closing of eyes when an object

moves towards them. Processed and integrated in

spinal cord and brainstem

b. Acquired or Conditional Reflex – Results from

practice and learning, e.g., steering car wheel to

follow a curve done automatically but after

considerable training effort. Integrated, processed

in higher brain centers.

Relfex Arc

- Basic unit of integrating neural activity; anatomical

basis for the reflex

- Stereotypical response to adequate stimuli

*Stereotypical response: generally involuntary

- May be innate or learned, but there are reflexes

that you NEED to learn (i.e. in driving).

- Simplest circuit involved for posture, walking,

eating, laughing as well as control of autonomic

functions.

-

*Bell-Magendie Law - Principle that states that the dorsal

(posterior) roots of the spinal cord are sensory and that the

ventral (anterior) roots are motor.

Reflex Arc (parts)

1. Afferent limb

- Would consist of a sensory receptor organ.

- Afferent or sensory neuron and nerve

- The sense organ may be part of the first order

neuron (free or encapsulated nerve endings) or a

specialized independent cell.

2. Center

- The afferent limb will synapse with one or more

neurons in CNS (either in the spinal cord,

brainstem, thalamic nuclei, or the cerebral cortex).

3. Efferent limb

- Efferent or motor neuron and nerve and an

effector organ (glands- exocrine and endocrine and

muscles – smooth, skeletal & cardiac)

- Efferent fiber that innervates skeletal muscle -

alpha (α) motor neurons (which is the FINAL

COMMON PATHWAY towards skeletal muscles!).

The soma of skeletal muscle neurons are found in

the ventral horn.

*Cardiac and smooth muscle have different fibers

(Autonomic nerves – parasympathetic or

sympathetic; pre- and post-ganglionic).

- Intrafusal fibers – gamma (γ) motor efferents

Reflex Arcs vary in complexity.

Simple at level of the spinal cord

More complex at the level of brainstem

Most complex in the cerebral cortex

Stimulus – a change in the external/internal environment.

In the body, changes in temperate, pressure, electrolyte

concentration, etc., can act as stimuli

Adequate Stimulus – a stimulus to which a receptor is most

sensitive or to which it has a low threshold, e.g., eye

sensitive to lights; see „stars‟ when punched.

Threshold Stimulus – the weakest stimulus that a sensory

receptor can reliably detect and activate primary afferent

fibers

Motor Unit – a single motor neuron and the muscle cells it

synapses on. Each muscle cell belongs to only one motor

unit. Size of motor units varies and depends on muscle

function: small muscle that generate very finely controlled

movements (e. extra-ocular muscles of the eyes, motor

units tend to be small and may contain just a few muscle

fibers); large muscles that generate strong forces, e.g.,

gastrocnemius muscle of the leg, tend to have large motor

units with more than several thousand muscle fibers.

Two Types of motor neurons:

a. Alpha Motor neurons – innervate the main force-

generating muscle fibers (“extrafusal” fibers).

b. Gamma Motor neurons – innervate only the fibers

of the muscle spindle (“intrafusal” fibers)

Motor Neuron Pool – the groups of all motor neurons

innervating a single muscle

**Not all reflex activity involves clear-cut reflex arcs:

- response may be mediated through neurons

or hormones or both

- local response may not be due to hormones

or nerves but by local metabolites

SUBJECT: PHYSIOLOGY

TOPIC: REFLEXES

LECTURER: DANTE G. SIMBULAN JR. PhD

DATE: FEBRUARY 2011


Classification Systems of Reflexes

A. According to NUMBER of SYNAPSES at level of the

SPINAL CORD:

1. Monosynaptic – only one synapse

2. Polysynaptic – two or more synapses in between your 1st

order neuron and your final common

pathway.

B. According to LOCATION of SENSORY RECEPTOR

1. Superficial – skin (cutaneous) and subcutaneous;; result

from stimulation of the receptors present in the skin and

mucous membrain – they are all polysynaptic, e.g.,

withdrawal reflex or scratch reflex.

2. Deep – deep tissues (i.e. muscle, bone, joints); reflexes

that result from stimulation of receptors present in muscles

or tendons, e.g., stretch reflex

3. Visceral – i.e. carotid sinus, carotid arch, baroreceptors,

chemoreceptors; clinically important reflexes

– micturation, defacation and erection.

C. According to LOCATION of EFFECTOR RESPONSE

1. Somatic – i.e. skeletal muscle contraction

2. Autonomic – i.e. tachycardia, bradycardia, increase in

stroke volume

*overlaps such as somato-autonomic (i.e. You get pinched

and then there is an increase in blood pressure aside from

the withdrawal response.)

D. According to SITE of INTEGRATION (in the CNS)

1. Spinal Cord

2. Brainstem

3. Thalamus

4. Hypothalamus

5. Cerebral Cortex (where most learned reflexes are

mediated)

TWO MAIN TYPES OF REFLEX ARCS:

1. Monosynaptic Reflex (e.g. stretch reflex of muscle

spindles) – made up of a two-neuron pathway from

receptor to effector (the afferent or sensory neuron has a

direct synaptic connection with the efferent / motor neuron,

without the intervention of interneurons), e.g., stretch or

myotactic reflex – which is the most rapid of all reflexes,

utilizing 1A afferent which are the largest diameter, fastest/

conducting of any afferent nerves

2. Polysynaptic Reflex / Multi-synaptic

- More than one synapse

- Made up of a few or several interneurons

intersposed between the afferent and efferent

neurons, e.g., withdrawal reflex

- i.e. pain reflex, inverse stretch (of golgi tendon),

and withdrawal flexor cross extensor reflexes

- Autonomic reflexes – cardiovascular baroreceptor

reflex (involving your pre- and post- synaptic

neurons). May elicit a cardioinhibitory response or

cardioaccelatory.

**In both mono- and polysynaptic arcs, the activity is

modified by such phenomena as spatial and temporal

summation, subliminal fringe effects, and other laws.

*A shows 3 interneurons; B shows 4 interneurons;

C shows 4 interneurons and a neuron that sends

fibers back.

Three Target Reflexes (examples of Spinal Reflexes)

A. Stretch or Myotatic Reflex – monosynaptic; the simplest

reflex; passively stretching a skeletal muscle causes a

reflexive contraction of that same muscle and relaxation of

the antagonistic muscle, e.g., “knee jerk or patellar reflex”

– a light tap on patellar tendon pulls on and briefly

stretches the quadriceps femoris muscles (an extensor)

reflexive contraction of quadriceps and relaxation of

semitendinosus muscle (a flexor). This is a key reflex that

helps maintain posture; most rapid of all reflexes, It has two

forms:

1. Phasic stretch Reflex – elicited by primary endings

of muscles spindles

2. Tonic stretch reflex – depends on both primary and

secondary endings

The stretch reflex is a monosynaptic reflex,mediated

by 1A and 2 sensory fibers emanating from the muscle

stretch receptor known as muscle spindles. Best studied in

decerebrate animals, also in spinal animals that have

recovered from spinal shock. Examples are seen in deep

tendon reflexes, such as the patellar reflex, Achilles reflex,

masseter, triceps, etc. The muscle that is stretched

contains sensory receptor known as the muscle spindle.

The muscle spindle elicits the reflex contraction

B. Inverse Stretch (or Inverse Myotatic) Reflex/ Autogenic

inhibition – di-, tri- synaptic reflex, extension of stretch

reflex, a.k.a. AUTOGENIC INHIBITION or LENGTHENING

REACTION (but may pertain to the pathologic response

secondary to spinal cord lesions).

- A relaxation in response to a stroing muscle

tension (muscle contraction stretches the tendon). The

receptor for the inverse stretch reflex is the golgi tendon

organ. The fibers from the golgi tendon organs make up the

1B group of myelinated, rapidly conducting sensory nerve

fibers. Stimulation of these 1B fibers leads to the

production of IPSPs on the motor neurons that supply the

muscle from which the fibers arise. The 1B fibers end on

the spinal cord on inhibitory interneurons that in turn

terminate directly on the motor neurons (they also make

excitatory connections with motor neurons supplying

antagonists to the muscle.) The inverse reflex is a by-

synaptic reflex.

C. Flexion Reflex – this is a polysynaptic reflex, This involves

many receptors outside of muscle that contracts.

Afferent volleys arising from activation of sensory receptors

cause:

1. Excitatory interneurons to activate alpha motor

neurons that supply flexro muscles in the

ipsilateral limb.


2. Inhibitory interneurons to prevent the activation of

alpha motor neurons that supply the antagonistic

extensor muscles

3. In addition, commissural interneurons evoke the

opposite pattern of activity in the contralateral side

of the spinal cord, This opposite pattern results in

extension, the Crossed Extension Reflex. The

contralateral effects helps the subject maintain

balance.

The most powerful flexion reflex is the flexor

Withdrawal reflex (a pain reflex):

-activated by nociceptors (nociceptors form the

afferent limb of this reflex; includes cutaneous, muscle,

joint and visceral nociceptor

- polysynaptic, flexor cross extensor and post-

synaptic reflex components)

-there is considerable divergence of the primary

afferent and interneuronal pathways in the flexion reflex

involving major joints in a limb, e.g., hip, knee, ankle, in a

strong flexor withdrawal reflex.

- most powerful flexison

* Both stretch and inverse stretch reflexes are stimulated

by proprioceptive stimuli.

SENSORY RECEPTOR OF DEEP REFLEXES

Muscle spindle

Golgi Tendon Organ

Muscle Spindle

- Wrapped around intrafusal fibers (which are

actually part of the muscle spindles which are a

type of skeletal muscle fiber)

- the contractile part of skeletal muscle fibers are

the EXTRAFUSAL FIBERS.

- Both the intrafusal and extrafusal fibers run

parallel with each other and have sensory endings

wrapped around them

- Histology: spindle-shaped, about 100 microns in

diameter, and up to 10 mm long. It lies freely in the

lymph space between regular extrafusal muscle fibers,

in parallel. Within a muscle spindle, there are two main

types of intrafusal fibers:

1. Nuclear bag fibers – with several nuclei in

central or equatorial region; generally two

nuclear bag fibers per muscle spindle

a. Nuclear bag fiber 1 has low level

of myosin ATPase activity

b. Nuclear bag fiber 2 has a high

level of myosin ATPase activity

2. Nuclear chain fibers – with one row of

nuclei; about 4 or more nucear chain

fibers per muscle spindle

Golgi Tendon Organ (GTO)

- Arranged in series with extrafusal fibers in the

junction area of muscle and tendon.

- Consist of a netlike collection of knobby nerve

endings among the fascicles of a tendon

- Arranged in series with the extrafusal fibers

- Formed by the terminals of group 1B afferent

fibers (also myelinated, rapidly conducting sensroy

nerve fibers)

- Stimulated by both passive stretch and active

contraction of the muscle; muscle contraction is

more effective than muscle stretch

- Signals force, rather than muscle length or rate of

change of muscle length

- This is the sensory receptor for the inverse stretch

reflex (myotatic reflex)

Mammalian Muscle Spindle

- Activates the stretch reflex

- Has a connective tissue capsule

- Intrafusal fibers

o Nuclear bag fibers (1-3) – have a highly

nucleated central part

o Nuclear chain fibers (3-9) – its nuclei form

a chain

- Sensory fibers/endings (histology)

o Group Ia (primary afferent)

Refers to an A-α sensory fiber

Fast conducting

Come from nuclear bag fiber, some

from chain

One branc of 1A fibers innervates

nuclear bag fiber 1; nne branch

innervates nuclear bag fiber 2 and

nuclear chain fibers

Group 1A fibers belong to the largest

diameter clas of sensory fibers and

conduct at 72-120 m/sec. Group 1A

fibers wrap around the center of the

nuclear bag and nuclear chain fibers

Annulospiral ending – sensory endings

that wrap around the intrafusal fibers

o Group II (Secondary afferent)

Fast conducting (not as fast as Ia)

Group II fibers are intermediate in size

and conduct at 36-72 m/sec.

Located near the ends of the intrafusal

fibers, mainly on nuclear chain fibers

(occasionally may contact a nuclear

bag fiber.

Nuclear chain fiber = terminate as a

flower spray ending

Muscle Spindle = Connective Tissue capsule + Sensory

endings + Intrafusal fibers


- Efferent limb

o Responsible for effector response of a

muscle spindle = REFLEX CONTRACTION.

- A γ fibers (γ efferents) – gamma motor neuron

o Come from spinal cord to innervate the

intrafusal fibers

o Motor innervation

o Tonically active to maintain muscle tone

o Discharge at resting rate

o Two Types:

Dynamic gamma motor axons –

end with plate endings on nuclear

bag fibers

Static Gamma motor axons end

with trail endings on nuclear

chain fibers;

*gamma motor axons are smaller in diameter than the

alpha-motor axons to extrafusal fibers, hence conduct more

slowly at 12-48 m/sec.

- Intrafusal fibers have a non-contractile portion

(sensory portion; central) meaning they DO NOT

have actin and myosin.

- Only terminal ends have contractile elements

innervated by γ efferents.

- When γ efferents discharge, the terminal ends

contract and the central portion is STRETCHED

(hence the name of the reflex).

*γ efferents are actually generally tonically active

to maintain muscle tone.

- γ efferents will increase discharge when you inhibit

the negative inhibition signals (or inhibitory

descending signals) coming from the brainstem.

DISINHIBITION happens and their basal discharge

increases. This happens most likely in spinal cord

lesions and leads to HYPEREFLEXIA (increased

sensitivity of the reflexes).

Length feedback system

In vitro setup

- In stretched muscle – sensory nerves increase in

discharge frequency (number of impulses).

- In stimulated muscle (contracted) – Ia and II fibers

are stretched, hence no impulses (but in reality,

there is no silencing since A γ fibers are tonically

active)

- 31% of motor fibers from ventral horn are γ

efferents

- ~70% are α motor neurons

Control of γ efferent Discharge

- Increased γ efferent discharge – while muscle is

not stretched (artificially stimulated in in vitro setup)

o There is stimulation of sensory afferents

- Increased γ efferent discharge – when muscle is

stretched

o Stronger reflex contraction (more impulses)

* If you severe your γ efferents, most likely your α motor

efferents are severed too because they are together in one

nerve bundle.

Role of Stretch reflex in Postural Reflexes

The upright posture characteristic of mas is

produced, maintained, and restored when upset, by a

series of coordinated reflexes called postural reflexes.

Posture depends on the degree and distribution of muscle


tone and muscle tone depends principally on stretch reflex,

hence, the stretch reflex is the basic postural reflex.

The role of stretch reflex in the maintenance of

posture is reinforced and modified by afferent impulses to

the CNS (central nervous system) from:

1. Proprioceptors of the muscles of the neck,

trunk and limbs

2. Eyes

3. Vestibular apparatus

4. Exteroceptors of the skin

These impulses are integrated by coordinated

activity of the spinal cord, brainstem, cerebellum,

basal ganglia and cerebral cortex. (neck muscles

contain the lasrgest concentration of muscles

spindles of any muscle in the body).

Reciprocal Innervation (Reciprocal Inhibition)

o Muscle agonists and antagonists (i.e. If

your muscle is the biceps brachii, your

antagonist is your triceps brachii.)

- Principle of Reciprocal Innervation in Stretch

reflexes

o Knee jerk reflex

Tap the quadriceps femoris tendon.

Hamstrings relax and quads contract.

The inhibitory interneuron (golgi bottle

neuron) receives an excitatory signal

from the afferent limb which therefore

inhibits the α motor neuron to

stimulate the hamstrings resulting into

reflex relaxation of the hamstrings.

*This inhibition happens by the release of glycine

(an inhibitory neurotransmitter) by the inhibitory

interneuron that leads to hyperpolarization of the

α motor neuron.

The α motor neuron to the quadriceps

femoris also receives an excitatory

signal and therefore causes

contraction of the muscle.

Both of these happen simultaneously

giving rise to the “knee jerk” action.

o Deep tendon reflexes – excitatory

monosynaptic reflex of the stretch reflex.

Refers to STRETCH REFLEX not

INVERSE STRETCH REFLEX. (Be

mindful of this because it is

misleading).

o Used to test patients with spinal cord

lesions.

Inverse Stretch Reflex and Golgi Tendon Organ

- a.k. a. the Inverse Myotactic Reflex

- Sensor for tension feedback

- Very responsive to forceful muscle contraction and

passive stretching.

- If you contract muscles too much or if you carry a

very heavy object your tendons might severe or

tear. There is a receptor similar to a pain receptor

(but does not respond to pain) that responds to

excessive forceful contractions.

- Anatomically the GTOs can be found at the junction

of tendon and muscle fibers

- Proportion is 1 GTO : 10-15 extrafusal fibers

- Again, stimulants are: passive stretching and

contraction

- Produces reflex relaxation brought about by

inhibitory interneuron which causes

hyperpolarization of the α motor neuron.

Other terms for inverse stretch reflex:

- Autogenic Inhibition – when there‟s passive

stretching or an increased muscle tension due to

forceful muscle contraction it will inhibit itself.

o Inhibition brought about by activity of the

muscle itself not the muscle concerned.

- Lengthening Reaction - results in a reflex

relaxation.

Central Connections

- Ib afferent from GTO

- Similar to interneuron found in reflex relaxation. In

fact, it might be one and the same, the only

difference is that it receives descending and/or

sensory inputs from periphery.

Polysynaptic Reflexes

- We‟ll focus on the Withdrawal Reflex which is a

pain reflex.

- But there are also many non-noxious reflexes (i.e.

itch)

Flexor Cross Extensor Reflex (Withdrawal reflex)

If you step on a broken bottle (“bubog”) there is:

o Contraction of hamstrings to evade

damaging stimulus (flexor component)

o Contraction of muscles on contralateral

side for balance (cross extensor

component)

- (+) Reciprocal Innervation

- Others:

o Muscle spasm, injured viscera, muscle

cramps

o Reflexes of posture and locomotion

o Scratch reflex – automatic response we

can automatically localize the stimulus.

With knowledge of the somatotropic

organization of the sensory homunculus

1

•DRG neuron releases an excitatory neurotransmitter: Glutamate)

2

•The inhibitory interneuron is depolarized and thus releases glycine (for inhibition).

3•The α motor neuron is inhibited.)

4

•Reflex relaxation (that is proportionate to amount of reflex contraction)

Releases glutamate (excitatory)

Releases glycine (inhibitory)

Inhibited = Reflex relaxation


we can localize the area of the stimulus.

*Not just a spinal reflex but it also has a

cerebral cortex component.

o Visceral autonomic reflexes

o Babinski Reflex – found in infants; upon

mechanical stimulation the baby‟s toes

turn downward (toe extension)

Due to underdeveloped pyramidal

fibers.

If this happens in adults, there is

a lesion in the CST or pyramidal

tract (upper motor neuron lesion).

o Suckling reflex – has somatic components

(neuroendocrine like oxytocin and

prolactin)

Also a superficial reflex

o Moro reflex – startling reaction in babies.

o Stepping reflex

Superficial Reflexes – elicited by stimulation of mucous

membrain and skin. They are all polysynaptic

(pleurisynaptic). They include:

1. Corneal Reflex

2. Snout Reflex

3. Rooting Reflex

4. Sucking Reflex

5. Abdominal Reflex

6. Plantar Reflex (all toes flex)

7. Cremasteric Reflex

8. Sphincter Reflex, etc.

**2, 3 and 4 - transposted abdominal muscle reflex,

absent in upper (suprasegmental) motor neuron lesions

Visceral Reflexes/ Other reflexes found in other organ

systtems

A. Cardiovascular System Reflexes

a. Bainbridge Reflex – right heart distention

increase heart rate; tachycardia caused

by an increase in venous return

b. Baroreceptor Reflex – increased right

atrial pressure increase in cardiac

output increase in arterial pressure;

increase in heart rate or relieving stretch

on high pressure arterial receptors

tachycardia, which increase stretch on

high pressure arterial receptors

decrease stroke volume (SV)

c. Starling‟s Law – decrease initial fiber

length decrease stroke volume and vice

versa

d. Chemoreceptor Reflex

e. Ventricular Receptor Reflex

f. Cushing Reflex – increase in arterial

presure occurs in response to an increase

in intracranial pressure

B.

Spinal Cord Transection

- Usually reflexes become hyperactive

(HYPEREFLEXIA) after recovery from spinal shock

(period of hyporeflexia).

- These hypereflexive responses can be utilized by

paraplegics with spinal cord transections to be

able to induce some actions that require voluntary

control or normal physiologic functions.

- “Mass reflexes” – involve hypereflexive responses.

o For example, the patient has a spinal cord

transaction at the level of T12, he can

simply pinch his leg to induce a mass

reflex.

o i.e. The patient wants to defecate (anal

sphincters have voluntary control), he can

pinch just pinch himself that will allow

them to empty their bowel in the toilet.

Two types of hypereflexia:

- ABNORMAL LENGTHENING REACTION (Clasp-knife

/ Swiss-knife reflex)

o Patients with upper motor neuron lesion

o At first there is resistance to stretch when

you bend a limb (knee/elbow) as a result

of stronger muscle contraction brought

about by stretching of the tendons when

you try to bend the limb.

o Hyperactive relfex due to disinhibition of γ

efferents (discharge more than normal)

due to loss of tonic inhibition of upper

motor neuron.

- CLONUS

o Also an example of increased γ efferent

discharge due to upper motor neuron

lesion

o Commonly seen in ankle reflex.

o In video: Try to stretch the gastrocnemius

but it is HYPERSPASTIC.

END OF TRANSCRIPTION

REPORTINGS: (Based on powerpoints of the reporters)

GLUTAMATE TRANSMITTER-RECEPTOR REACTION

- transmitter-receptor interaction

- Central Pain pathways

- Neurotransmitter released : glutamate, substance

P, and CGRP to excite the 2nd order neurons in the

dorsal horn and trigeminal nucleus .

GLUTAMATE

- is one of the 20 amino acids used to assemble

proteins and as a result is abundant in many areas

of the body.

- the most prominent neurotransmitter in the body,

being present in over 50% of nervous tissue.

- Note: The only direct effect of a neurotransmitter is

to activate one or more types of receptors.

GLUTAMATE RECEPTOR

- are synaptic receptors located primarily on the

membranes of neuronal cells.

- responsible for the glutamate-mediated post-

synaptic excitation of neural cells

- important for neural communication, memory

formation, learning, and regulation. (See

supplementary figures on following page.)

- are thought to be responsible for the reception and

transduction of umami taste stimuli.

- Taste receptors of the T1R family, belonging to the

same class of GPCR as metabotropic Glutamate

Receptors are involved

- Additionally, the mGluRs as well as ionotropic

glutamate receptors in neural cells have been

found in taste buds and may contribute to the

umami taste

During Fast Pain Response

- C-Fiber excitation releases Glutamate and

Aspartate

During Slow Pain Response

http://en.wikipedia.org/wiki/Transmembrane_receptor

http://en.wikipedia.org/wiki/Neuron

http://en.wikipedia.org/wiki/Umami


- in prolonged stimulation, Neuropeptides are

released by the C-Fibers such as Substance-P

GLUTAMATE vs. SUBSTANCE P

GLUTAMATE

o fast excitatory synapses in the brain and

spinal cord.

o It is also used at most synapses that are

"modifiable", i.e. capable of increasing or

decreasing in strength.

o Modifiable synapses are thought to be the

main memory-storage elements in the

brain.

SUBSTANCE P

o is an undecapeptide responsible for

transmission of pain from certain sensory

neurons to the central nervous system.

o Substance P also stimulates mast cells to

release more histamine as well as more

prostaglandins and bradykinins, further

stimulating the nociceptors.

o Substance P also contributes to swelling

and redness in the area of pain.

GLYCINE TRANSMITTER-RECEPTOR REACTION

GLYCINE

- is the simplest of amino acids, consisting of an

amino group and a carboxyl (acidic) group attached

to a carbon atom.

- It is one of the non-essential amino acids.

- Some of its main functions include being a

precursor to proteins and a neurotransmitter in

vertebrate CNS.

- It has excitatory (in the forebrain) and mainly

inhibitory (in spinal cord and brainstem) actions.

- The excitatory function of the glycine

neurotransmitter is the coagonist of glutamate N-

methyl-D-aspartate (NMDA) subtype of glutamate

receptor.

- Formed from Serine by Serine

hydroxymethyltransferase (SHMT)

- Packaging to synaptic vesicles by H+ dependent

vesicular inhibitory amino acid transporter (VIAAT)

- Glycine release depends on Ca2+ concentration (2

figures)

AGONISTS ANTAGONISTS

B-Alanine Styrchnine

Taurine Picrotoxin

Proline Caffeine

L-Serine

- Styrchnine binds to the glycine receptor without

opening the chloride ion-channel; it inhibits

inhibition.

- Styrchnine poisoning leads to muscular tetany.

GLYCINE RECEPTOR (GlyR)

- Ligand-gated ion channel

- Pentameric (250 kDa):

o 4 α- subunits (48 kDa)

Ligand-binding site

o 1 β- subunit (58 kDa)

o Both subunits:

Span the post-synaptic

membrane and are glycosylated.

o Composed of 4 hydrophobic segments:

M1-M4; as alpha-helices.

GEPHYRIN

- Links GlyR to the intracellular cytoskeleton

- Profilin

- Collybistin

- Raft-1 – candidate regulator of dendritic protein

synthesis

- Aggregates GlyR in clusters

GLYCINE TRANSPORTER (GlyT)

- Na+/Cl--dependent, high-affinity glycine

transporters

- Facilitates termination of Glycine synaptic actions

by rapid reuptake

GlyT1

- Found in the plasmalemma of Astrocytes; involved

in removal of glycine from post-synatic receptors

(Involved in actin dynamics and

downstream signaling )


GlyT2

- Found in the pre-synaptic membrane; replenishes

the presynaptic glycine pool

FIGURES FOR GLUTAMATE:


FIGURES FOR GLYCINE:

Glycine potentiate the

effects of Glutamate as

an excitatory

neurotransmitter of the

NMDA receptor in the

forebrain.


Formation of Glycine

Glycine Release


GLYCINE TRANSMITTER-RECEPTOR INTERACTION

(Summary)

1. Glycine is produced from precursor: Serine by SHMT

(Serine hydroxymethyltransferase).

2. Then, packaging to synaptic vesicles is by H+ dependent

vesicular inhibitory amino acid transporter (VIAAT).

3. The release of Glycine depends on Ca2+ concentration.

4. When released into a synapse, glycine binds to a

receptor which makes the post-synaptic membrane more

permeable to Cl- ion.

5. This hyperpolarizes the membrane, making it less likely

to depolarize and generate an action potential. Thus,

glycine is an inhibitory neurotransmitter.

6. It is de-activated in the synapse by a simple process of

reabsorption by active transport back into the pre-synaptic

membrane (providing a substrate for the VIAAT) or glial

system (for degradation by the Glycine, GCS).

Glycine receptor is a complex of a glycine-recognition site and an associated Chloride channel. At least 2 glycine

molecules are needed to bind with the receptor to activate and open the Chloride channel.

Here, you can see that the GlyT1 and GlyT2 transporters are found in glial and pre-synaptic terminals, respectively.

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Physiology - Reflexes