Neurotransmitters

Definition
“Neurotransmitter is a chemical substance that acts as the mediator for the transmission of impulse from one neuron to another neuron through synapse”
 Transmission of information at chemical synapse involves:-
1. Release of neurotransmitter from presynaptic terminal
2. Diffusion across synaptic cleft
3. Binding to specific receptors to produce EPSP or IPSP

Classification of Synaptic Transmitters

A. Rapidly Acting Transmitters

Small molecules (Neurotransmitters)
Class I : Acetyl Choline
Class II : Amines:
NE, Epi, Dopamine, Serotonin, Histamine
Class III : Amino Acids:
GABA, Glycine, Glutamate, Aspartate.
Class IV : Nitric Oxide (NO)

B. Slowly Acting Transmitters (Neuropeptides)

a. Hypothalamic Releasing Hormones:
TRH, LHRH, GHIH (Somatostatin)
b. Pituitary Peptides:
ACTH, β-Endorphin, α-MSH, PRL, LH, TSH, GH, Vasopressin, Oxytocin.
c. Peptides Acting on Gut & Brain:
Leucin enkephalin, Methionine enkephalin,Subs P, Gastrin, CCK, VIP, Nerve GF, Brain derived neurotropic factors, Neurotrensin, Insulin, Glucagon.
d. From other Tissues:
Ag-II, Bradykinin, Carnosine, Sleep peptides, Calcitonin

Characteristics

Small Mol. Wt
 Rapidly Acting (In milliseconds)
* by activation of Receptor Proteins
* by opening/closing the ion channels
(i.e. development of EPSP or IPSP)
 Produce Acute Response in CNS (i.e. Sensory signals or Motor signals)
 Synthesized in Cytosol of presynaptic terminals & stored in presynaptic vesicles
 Released (In milliseconds) into synaptic cleft upon arrival of A.P
 Fate :
1. Broken by enzyme in synaptic cleft
2. Uptake by presynaptic terminal (Active transport) or by Neuroglia

Neuropeptides (Characteristics)

Large Mol Wt
 Slowly Acting
 Produce Prolong Actions by long term :
1. changes in no. of receptors
2. opening / closing of ion channels
3. changes in no. of synapses & in size of synapses
4. changes in metabolic machinery
5. changes in specific Genes
 Not Synthesized in Cytosol of presynaptic terminals but
synthesized in Ribosomes, ER, Golgi Apparatus of Soma
 Axonal Streaming @ few cm/day.
 Released ( a few vesicles) in response to AP.
 Vesicles are autolyzed not reused.
 Thousands (or more) times potent than Neurotransmitters.

Special Characteristics of Synaptic Transmission

1. One way conduction (Bell- Magendie Law)

 Impulses are transmitted in one direction in chemical synapses i.e. from presynaptic neuron to postsynaptic neuron

 Impulses can be conducted in either direction in electrical synapses

2. Summation

Simultaneous discharge of many presynaptic terminals at the same time or in rapid succession to produce an action potential
a. Spatial summation:-
Activation of many presynaptic terminals on widely spaced areas
b. Temporal summation:-
Successive/repeated discharge of a single presynaptic terminal

3. Facilitation/Augmentation/ Post tetanic potentiation

1. Successive stimulation of neuron may build up summated postsynaptic potential (EPSP) which reaches firing level
2. Due to release of neurotransmitter + Accumulation of Ca++ in presynaptic terminal etc.
3. Neuron is said to be facilitated when its membrane potential is nearer the threshold from firing than normal but not yet the firing level.

4. Presynaptic & Postsynaptic Inhibition

   i. Postsynaptic Inhibition: or Direct Inhibition
    Due to release of inhibitory neuro transmitter
   e.g. GABA, Glycine
   * K+ out flux & Cl- influx
   * Hyper polarization or Negativity inside i.e. IPSP
   ii. Presynaptic Inhibition or Indirect Inhibition
    Release of an inhibitory substance onto the outside of presynaptic nerve fibrils before their own axon terminate on postsynaptic neuron.
   e.g. GABA opens Cl- channels (Cl- influx into terminal fibril)
   Inhibits synaptic transmission
    Occurs in sensory pathways; to minimize sideway spread
   & mixing of signals in sensory tracts

5. Electrotonic Conduction:

Loss of large share of EPSP before it reaches soma is due to :
1. Long dendrites
2. Leakiness to electrical current

a. Thin membranes
b. Partially permeable to K + & Cl

6. Fatigue of Synaptic Transmission

 Progressive reduction in firing rate of postsynaptic neuron due to repetitive stimulation of excitatory synapses at a rapid rate
 A protective mechanism against excess neural activity
e.g. epileptic seizure
 Mechanism :
a. Exhaustion (Partial) of stores of transmitter in presynaptic terminal
b. Progressive inactivation of postsynaptic receptors
c. Slow development of abnormal conc. of ions inside postsynaptic terminal

7. Effect of Acidosis or Alkalosis

 Alkalosis :
Increased neuronal activity (pH 7.8 – 8.0 , Epileptic seizure)
 Acidosis :
Decreased neuronal activity (pH < 7.0, Coma)
e.g. Diabetes mellitus, Uremia

8. Effect of Hypoxia

 Neuronal excitability is highly dependent on normal supply of O2
 Cessation of brain’s blood flow for 3-7 sec leads to unconsciousness i.e. complete inexcitability of some of the neurons.

9. Effect of Drugs

 Caffeine (Coffee)
 Theophylline (Tea)
 Theobromine (Cocoa)

Produce increased neuronal  excitability by decreasing Threshold for excitation

Strychnine causes increased neural excitability by inhibiting normal inhibitory substance
e.g. Glycine in spinal cord.
 Most anesthetics cause increased neuronal membrane threshold i.e. decreased synaptic transmission.

10. Synaptic Delay (Normal= 0.5 msec)

“Minimal period required during transmission of signal
from presynaptic neuron to postsynaptic neuron”.

How occurs? Time spent on following events:
1. Discharge of synaptic transmitter
2. Diffusion of transmitter
3. Action of transmitter
4. Change in permeability of membrane
5. Conductance of ions e.g. Na+ Influx leading to EPSP

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