DISORDERS OF SYNAPSES BY

DR IRAM SADDIQA AAMIRASSOCIATE PROFESSOR

BUMDC KARACHI

LEARNING OBJECTIVES At the end of lecture, student should be able to:• DEFINE SYNAPSE.• CLASSIFY SYNAPSE: ANATOMICAL AND

PHYSIOLOGICAL• DESCRIBE PHYSIOLOGICAL ANATOMY OF

SYNAPSE.• ENLIST THE DRUGS MODIFYING TRANSMISSION

BY ACTING ON PRESYNAPTIC MEMBRANE, SYNAPSE AND POST SYNAPTIC MEMBRANE

• ENLIST DRUGS THAT ENHANCE OR BLOCK TRANSMISSION AT THE NEUROMUSCULAR JUNCTION

• DESCRIBE THE EFFECTS OF VARIOUS TOXINS ON SYNPATIC TRANSMISSION

What is a synapse?A junction where the axon or some other portion of one cell (presynaptic cell) terminates on the dendrites, soma, or axon of another neuron (post synaptic cell). The term was introduced in nineteenth century by the British neurophysiologist Charles Sherrington

The Sanger Institute

SYNAPSESELECTRICAL SYNAPSES Open fluid channels that

conduct electricity from one cell to next.gap junctions Two way conduction.Less time consuming.eg: Smooth mus: & cardiac mus: in the CNS:

Arousal from sleep Mental attention Emotions and memory

CHEMICAL SYNAPSES Almost all synapses of

CNS.Typically composed of

two parts: Axonal terminal of the

presynaptic neuron, which release neurotranmitter.

Receptor region on the postsynaptic neuron.

NEUROMUSCULAR JUNCTION

Functional Anatomy of a Synapse

The neuromuscular junction is a synapse The motor end plate

is the terminal button of a motor neurone that makes contact with a muscle cell

The motor end plate releases the neurotransmitter acetylcholine that ultimately causes the muscle cell to contract

© 2008 Paul Billiet ODWS

DRUGS THAT ENHANCE OR BLOCK TRANSMISSION AT NM JUNCTION1. DRUGS THAT STIMULATE THE MUSCLE

FIBERS LIKE ACETYLCHOLINE LIKE ACTION

Methacholine

Carbachol

Nicotine

2. DRUGS THAT ACT ON SYNAPSE AND STIMULATE NEUROMUSCULAR JUNCTION BY INACTIVATING ACETYLCHOLINESTERASE NEOSTIGMINEPHYSOSTIGMINEDIISOPROPYL FLUOROPHOSPHATE

3. DRUGS THAT BLOCK TRANSMISSION AT NM JUNCTION

D TUBOCURARINE CURARE LIKE DRUGS

MYASTHENIA GRAVIS

TOXINS ACTING PRESYNAPTICALLYBLOCK THE RELAEASE OF NEUROTRANSMITTERS

Synaptobrevin and SNAP-25 are targets of

the clostridial neurotoxins: tetanus toxin acts in the Central Nervous System (CNS) and botulinum toxin acts at neuromuscular synapses – paralysis is caused by blockage of transmitter release.

Neurexin is targeted by a-latrotoxin, the black widow spider toxin, which induces massive transmitter release independent of Ca++ levels.

TETANUS TOXOID

BOTULINUM TOXINS B D F AND G

BOTULINUM TOXIN C

EFFECT OF ALKALOSIS ON SYNAPTIC TRANSMISSION

Normally, alkalosis greatly increases neuronal excitability. For instance, a rise in arterial blood pH from the 7.4 norm to 7.8 to 8.0 often causes cerebral epileptic seizures because of increased excitability of some or all of the cerebral neurons. This can be demonstrated especially well by asking a person who is predisposed to epileptic seizures to overbreathe. The overbreathing blows off carbon dioxide and therefore elevates the pH of the blood momentarily

EFFECT OF ACIDOSIS ON SYNAPTIC TRANSMISSION

Conversely, acidosis greatly depresses neuronal activity; A fall in pH from 7.4 to below 7.0 usually causes a comatose state. For instance, in very severe diabetic or uremic acidosis, coma virtually always develops.

FACTORS EFFECTINF SYNAPATIC TRANSMISSION: DRUGS

Many drugs are known to increase the excitability of neurons, and others are known to decrease excitability. For instance, Caffeine, Theophyline, Theobromine, which are found in coffee, tea, and cocoa, respectively, All increase neuronal excitability, presumably by reducing the threshold for excitation of neurons.