BY TARIQ MAHMOOD

NERVE TRANSMISSION
NERVE TRANSMISSION CAN BE DIVIDED INTO TWO PARTS:-

1) THE TRANSMISSION OF THE IMPULSE ALONG THE AXON UPTO THE SYNAPSE.

2) TRANSMISSION OF THE IMPULSE FROM THE PRE SYNAPTIC END TO THE POST SYNAPTIC END.

A NEURON

PHYSIOLOGICAL ASPECT OF NERVE TRANSMISSION

THE RESTING POTENTIAL OF THE NEURON.
y THE NEURON IN ITS NATIVE RESTING STATE HAS A NEGATIVE POTENTIAL ACROSS ITS MEMBRANE.THIS POTENTIAL IS OF THE ORDER OF -70 mv. y THIS NEGATIVE POTENTIAL IS MAINTAINED BY THE NET LOSS OF CATIONS FROM INSIDE THE CELL BY THE NA/K ATPASE AND THE ANIONS INSIDE THE CELL MEMBRANE.

MAINTAINENCE OF RESTING POTENTIAL ACROSS THE MEMBRANE OF THE NEURON.

NERVE RESTING POTENTIAL
NA/K ATPASE

STIMULATION OF A NEURON
y ON STIMULTAION OF A NEURON EITHER BY ELECTRICAL STIMULUS OR BY CHEMICAL STIMULATION IN FORM OF NEURO TRANSMITTORS THERE IS AN OPENING OF VOTAGE GATED OR NEUROTRANSMITTER GATED ION CHANNELS y WHEN THIS STIMULATION IS STRONG ENOUGH IT SETS UP A PROPOGATING CURRENT IT IS CALLED A THRESHOLD STIMULUS.

STIMULATION OF NEURONS BY MEANS OF NEUROTRANSMITTERS

THE RESTING MEMBRANE POTENTIAL,THRESHOLD STIMULUS,ACTION POTENTIAL.

PROPOGATION OF STIMULUS ALONG THE AXON

TRANSMISSION AT THE SYNAPSE

SYNAPTIC TRANSMISSION
y SYNAPSES ARE SPECIALIZED JUNCTIONS THROUGH WHICH

NEURONS SIGNAL TO EACH OTHER AND TO NON-NEURONAL CELLS SUCH AS THOSE IN MUSCLES OR GLANDS. THESE SYNAPSES ARE ESSENTIALLY CHEMICAL IN NATURE. INTERCONNECTED CIRCUITS WITHIN THE CENTRAL NERVOUS SYSTEM.

y CHEMICAL SYNAPSES ALLOW NEURONS TO FORM

y THEY PROVIDE THE MEANS THROUGH WHICH THE NERVOUS

SYSTEM CONNECTS TO AND CONTROLS THE OTHER SYSTEMS OF THE BODY, FOR EXAMPLE THE SPECIALIZED SYNAPSE BETWEEN A MOTOR NEURON AND A MUSCLE CELL IS CALLED A NEUROMUSCULAR JUNCTION.

ELEMENTS INVOLVED AT THE SYNAPTIC JUNCTION

ELECTRONMICROSCOPIC PHOTOGRAH OF A SYNAPSE

EVENTS AT THE PRESYNAPTIC MEMBRANE

MECHANISM OF RELEASE OF NEUROTRANSMITTERS INTO SYNAPTIC CLEFT

ACTION OF NEUROTRANSMITTERS AT POSTSYNAPTIC MEMBRANE

y AT THE POST SYNAPTIC MEMBRANE THERE EXIST

RECEPTORS FOR THE NEUROTRANSMITTERS RELAESED FROM THE PRE SYNAPTIC MEMBRANE.THESE RECEPTOR ATTACH THE NEUROTRANSMITTER MOLECULES AND PROPOGATE THE ACTION POTENTIAL IN THE POST SYNAPTIC NEURON OR OTHER CELLS.
y THESE RECEPTORS R OF TWO TYPES

IONOTROPIC RECEPTORS 2) METABOTROPIC RECPTORS

1)

MECHANISM OF IONOTROPIC RECEPTORS

MECHANISM OF ACTION OF METABOTROPIC RECEPTORS

MECHANISM OF DEPOLARISATION AT POST SYNAPTIC MEMBRANE(EPSP)

MECHANISM OF HYPERPOLARISATION AT POST SYNAPTIC MEMBRANE(IPSP)

MECHANISM OF HYPERPOLARISATION AT POST SYNAPTIC MEMBRANE(IPSP)

MECHANISM OF REGULATION OF NEUROTRANSMITTER RELEASE

y NEUROTRANSMITTER RELAESED IS AUTOREGULATED I.E. THE NEUROTRANSMITTER REGULATES ITS OWN RELAESE BY MEANS OF A FEEDBACK MECHANISM. y ON THE PRESYNAPTIC MEMBRANE THERE OCCUR NEUROTRANSMITTER RECEPTORS WHICH BIND TO THE NEUROTRANSMITTER RELEASED AND PREVENT FURTHER OPENING OF PRESYNAPTIC VESICLES INTO THE SYNAPTIC CLEFT.

FATE OF NEUROTRANSMITTERS IN SYNAPTIC CLEFT

BIOCHEMISTRY OF NEUROTRANSMITTERS
y BEFORE A SUBSTANCE CAN BE CALLED A NEUROTRANSMITTER:

1. PRESYNAPTIC TERMINAL SHOULD CONTAIN A STORE OF THE SUBSTANCE (PREFERABLY IN A SEQUESTERED FORM) 2. APPLYING THE SUBSTANCE TO A POSTSYNAPTIC CELL SHOULD MIMIC THE EFFECTS CAUSED BY STIMULATING THE PRESYNAPTIC TERMINAL

3. IF A DRUG IS KNOWN TO BLOCK A NEUROTRANSMITTER, IT SHOULD HAVE THE SAME EFFECT ON THIS TRANSMITTER IF IT S APPLIED EXOGENOUSLY 4. A MECHANISM FOR THE SYNTHESIS OF THIS TRASMITTER MUST EXIST (INCLUDING THE APPROPRIATE PRECURSORS/ENZYMES IN THE TERMINAL) 5. A MECHANISM FOR INACTIVATION OF THE TRANSMITTER MUST EXIST (CATABOLIC ENZYMES FOR ITS DEGRADATION/ REUPTAKE SYSTEM, ETC)

TYPES OF NEUROTRANSMITTERS

y ACETYLCHOLINE y SEROTONIN y GABA y DOPAMINE y NOREPINEPHRINE y ENDORPHINS

ACETLYCHOLINE
y ACETYLCHOLINE (ACH) IS A SIMPLE MOLECULE

SYNTHESIZED FROM CHOLINE AND ACETYL-COA THROUGH THE ACTION OF CHOLINE ACETYLTRANSFERASE.
y NEURONS THAT SYNTHESIZE AND RELEASE ACH

ARE TERMED CHOLINERGIC NEURONS

ACETYLCHOLINE SYNTHESIS

y ONCE RELEASED, ACH MUST BE REMOVED RAPIDLY IN ORDER TO ALLOW REPOLARIZATION TO TAKE PLACE; THIS STEP, HYDROLYSIS, IS CARRIED OUT BY THE ENZYME, ACETYLCHOLINESTERASE. THE ACETYLCHOLINESTERASE FOUND AT NERVE ENDINGS IS ANCHORED TO THE PLASMA MEMBRANE THROUGH A GLYCOLIPID.

ACETYLCHOLINE RECEPTORS
y ACH RECEPTORS ARE LIGAND-GATED CATION

CHANNELS COMPOSED OF FOUR DIFFERENT POLYPEPTIDE SUBUNITS ARRANGED IN THE FORM [(A2)(B)(G)(D)].
y TWO MAIN CLASSES OF ACH RECEPTORS

HAVE BEEN IDENTIFIED: 1)THE MUSCARINIC RECEPTORS 2)THE NICOTINIC RECEPTORS.

ACETLYCHOLINE RECEPTOR

CATECHOLAMINES
y THE PRINCIPAL CATECHOLAMINES ARE NOREPINEPHRINE,

EPINEPHRINE AND DOPAMINE.

y THESE COMPOUNDS ARE FORMED FROM

PHENYLALANINE AND TYROSINE. TYROSINE IS PRODUCED IN THE LIVER FROM PHENYLALANINE THROUGH THE ACTION OF PHENYLALANINE HYDROXYLASE. THE TYROSINE IS THEN TRANSPORTED TO CATECHOLAMINESECRETING NEURONS WHERE A SERIES OF REACTIONS CONVERT IT TO DOPAMINE, TO NOREPINEPHRINE AND FINALLY TO EPINEPHRINE

CATECHOLAMINE SYNTHESIS

ACTIVITY OF CATECHOLAMINES
y CATECHOLAMINES EXHIBIT PERIPHERAL NERVOUS SYSTEM EXCITATORY AND INHIBITORY EFFECTS AS WELL AS ACTIONS IN THE CNS SUCH AS RESPIRATORY STIMULATION AND AN INCREASE IN PSYCHOMOTOR ACTIVITY. y THE EXCITATORY EFFECTS ARE EXERTED UPON SMOOTH MUSCLE CELLS OF THE VESSELS THAT SUPPLY BLOOD TO THE SKIN AND MUCOUS MEMBRANES.

y CARDIAC FUNCTION IS ALSO SUBJECT TO EXCITATORY EFFECTS, WHICH LEAD TO AN INCREASE IN HEART RATE AND IN THE FORCE OF CONTRACTION. y INHIBITORY EFFECTS, BY CONTRAST, ARE EXERTED UPON SMOOTH MUSCLE CELLS IN THE WALL OF THE GUT, THE BRONCHIAL TREE OF THE LUNGS, AND THE VESSELS THAT SUPPLY BLOOD TO SKELETAL MUSCLE

y IN ADDITION TO THEIR EFFECTS AS NEUROTRANSMITTERS, NOREPINEPHRINE AND EPINEPHRINE CAN INFLUENCE THE RATE OF METABOLISM. THIS INFLUENCE WORKS BOTH BY MODULATING ENDOCRINE FUNCTION SUCH AS INSULIN SECRETION AND BY INCREASING THE RATE OF GLYCOGENOLYSIS AND FATTY ACID MOBILIZATION.

CATECHOLAMINE RECEPTORS

MECHANISMS OF ACTION OF CATECHOLAMINE RECEPTORS

SEROTONIN
y SEROTONIN (5-HYDROXYTRYPTAMINE, 5HT) IN ITS GREATEST CONCENTRATION (90%) IS FOUND IN THE ENTEROCHROMAFFIN CELLS OF THE GASTROINTESTINAL TRACT. MOST OF THE REMAINDER OF THE BODY'S 5HT IS FOUND IN PLATELETS AND THE CNS. y THE EFFECTS OF 5HT ARE FELT MOST PROMINENTLY IN THE CARDIOVASCULAR SYSTEM, WITH ADDITIONAL EFFECTS IN THE RESPIRATORY SYSTEM AND THE INTESTINES. VASOCONSTRICTION IS A CLASSIC RESPONSE TO THE ADMINISTRATION OF 5HT.

SYNTHESIS AND METABOLISM OF SEROTONIN

y THE FUNCTION OF SEROTONIN IS EXERTED UPON ITS

INTERACTION WITH SPECIFIC RECEPTORS. SEVERAL SEROTONIN RECEPTORS HAVE BEEN CLONED AND ARE IDENTIFIED AS 5HT1, 5HT2, 5HT3, 5HT4, 5HT5, 5HT6, AND 5HT7. 5HT1D, 5HT1E, AND 5HT1F. THERE ARE THREE 5HT2 SUBTYPES, 5HT2A, 5HT2B, AND 5HT2C AS WELL AS TWO 5HT5 SUBTYPES, 5HT5A AND 5HT5B.

y WITHIN THE 5HT1 GROUP THERE ARE SUBTYPES 5HT1A, 5HT1B,

y THE 5HT6 AND 5HT7 RECEPTORS ARE DISTRIBUTED

THROUGHOUT THE LIMBIC SYSTEM OF THE BRAIN AND THE 5HT6 RECEPTORS HAVE HIGH AFFINITY FOR ANTIDEPRESSANT DRUGS. THAT AFFECT THE ACTIVITIES OF EITHER ADENYLATE CYCLASE OR PHOSPHOLIPASE CG.

y MOST OF THESE RECEPTORS ARE COUPLED TO G-PROTEINS

SERTONIN RECEPTORS

GABA
y SEVERAL AMINO ACIDS HAVE DISTINCT EXCITATORY OR INHIBITORY EFFECTS UPON THE NERVOUS SYSTEM. THE AMINO ACID DERIVATIVE, GAMINOBUTYRATE, ALSO CALLED 4-AMINOBUTYRATE, (GABA) IS A WELL-KNOWN INHIBITOR OF PRESYNAPTIC TRANSMISSION IN THE CNS, AND ALSO IN THE RETINA. y NEURONS THAT SECRETE GABA ARE TERMED GABAERGIC

SYNTHESIS OF GABA
y GABA IS SYNTHESISED BY DECARBOXYLATION OF GLUTAMATE.

GABA RECEPTORS
y GABA EXERTS ITS EFFECTS BY BINDING TO TWO DISTINCT RECEPTORS, GABA-A AND GABA-B. THE GABA-A RECEPTORS FORM A CL- CHANNEL. y THE BINDING OF GABA TO GABA-A RECEPTORS INCREASES THE CL- CONDUCTANCE OF PRESYNAPTIC NEURONS. y THE GABA-B RECEPTORS ARE COUPLED TO AN INTRACELLULAR G-PROTEIN AND ACT BY INCREASING CONDUCTANCE OF AN ASSOCIATED K+ CHANNEL.

GABA A RECEPTOR

THANK YOU