physiology 1 lecture 14 synaptic transmission. n objectives: the student should know –1. the types...

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PHYSIOLOGY 1 PHYSIOLOGY 1 LECTURE 14 LECTURE 14 SYNAPTIC TRANSMISSION SYNAPTIC TRANSMISSION

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PHYSIOLOGY 1PHYSIOLOGY 1

LECTURE 14LECTURE 14

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSION

SYNAPTIC SYNAPTIC TRANSMISSIONTRANSMISSION

Objectives: The student should Objectives: The student should knowknow– 1. The types of synapses, electrical 1. The types of synapses, electrical

and chemicaland chemical– 2. The structure and function of 2. The structure and function of

synapsessynapses– 3. Neurotransmitters, types, 3. Neurotransmitters, types,

synthesis and removalsynthesis and removal

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSION Synapses are one of the means by Synapses are one of the means by

which excitable cells communicate with which excitable cells communicate with one another. Nerve to nerve synapse, one another. Nerve to nerve synapse, nerve to muscle - neuromuscular nerve to muscle - neuromuscular junction, and nerve to gland - junction, and nerve to gland - neuroglandular junctionneuroglandular junction

There are two general types of There are two general types of synapsessynapses– Electrical Synapses (Gap Junctions)Electrical Synapses (Gap Junctions)– Chemical Synapses (Neurological)Chemical Synapses (Neurological)

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONTYPES of SYNAPSESTYPES of SYNAPSES

Electrical SynapsesElectrical Synapses - - 1. Characteristics of electrical synapses1. Characteristics of electrical synapses

– a. Gap junctionsa. Gap junctions– b. Cytoplasmic continuity - direct ionic b. Cytoplasmic continuity - direct ionic

pathway cell to cellpathway cell to cell– c. No delay in transmission of the APc. No delay in transmission of the AP– d. Can be unidirectional or bidirectionald. Can be unidirectional or bidirectional– e. Locations - cell membrane to cell e. Locations - cell membrane to cell

membrane protein interconnectionmembrane protein interconnection

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONTYPES of SYNAPSESTYPES of SYNAPSES

2. Types of Electrical Synapses (2)2. Types of Electrical Synapses (2)– a. Non-rectifying (bidirectional) a. Non-rectifying (bidirectional)

electrical synapses - open channel electrical synapses - open channel between cellsbetween cells

– b. Rectifying (unidirectional) b. Rectifying (unidirectional) electrical synapse - one way trafficelectrical synapse - one way traffic

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONElectrical SynapseElectrical Synapse

Nonrectifying Nonrectifying Electrical SynapseElectrical Synapse - -

This is a simple gap This is a simple gap junction which when junction which when open connects cells open connects cells cytosol to cytosol. cytosol to cytosol. Ions can move freely Ions can move freely back and forth back and forth between cells, between cells, hence, action hence, action potentials.potentials.

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONElectrical SynapsesElectrical Synapses

Rectifying Electrical Rectifying Electrical Synapse -Synapse -

Because of the Because of the nature of the nature of the proteins making up proteins making up these gap junctions these gap junctions ions may only move ions may only move in one direction - in one direction - Example - From cell Example - From cell A to Cell B but not A to Cell B but not the reversethe reverse

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONElectrical SynapsesElectrical Synapses

Cytoplasmic Cytoplasmic Continuity -Continuity -

Gap junctions allow Gap junctions allow closely aligned cells closely aligned cells to communicate to communicate cytoplasm to cytoplasm to cytoplasm by cytoplasm by exchanging ions and exchanging ions and other other dissolveddissolved particles up to about particles up to about 1500 mol. weight.1500 mol. weight.

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

B. Chemical SynapsesB. Chemical Synapses Important characteristics ---Important characteristics --- 1. one way transmission1. one way transmission 2. time delay2. time delay 3. exocytosis3. exocytosis 4. diffusion4. diffusion 5. receptor activation5. receptor activation

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

Anatomy of a SynapseAnatomy of a Synapse– 1. Neuron structures - dendrites, 1. Neuron structures - dendrites,

soma (body), axon, terminal end or soma (body), axon, terminal end or bouton, and axon hillockbouton, and axon hillock

– 2. Synapse2. Synapse a. Axosomatic synapsea. Axosomatic synapse b. Axodendritic synapseb. Axodendritic synapse c. Axoaxonic synapse (always c. Axoaxonic synapse (always

inhibitory)inhibitory)

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

B. Pattern of Chemical Synaptic B. Pattern of Chemical Synaptic TransmissionTransmission– 1. Distinct separation of presynaptic and 1. Distinct separation of presynaptic and

postsynaptic cellspostsynaptic cells– 2. Can synapse on dendrites, soma, or axon2. Can synapse on dendrites, soma, or axon– 3. Nerves usually synapse with more than 3. Nerves usually synapse with more than

one nerve normally many nervesone nerve normally many nerves– 4. AP in presynaptic cell converted to 4. AP in presynaptic cell converted to

chemical signalchemical signal– Postsynaptic membrane receives chemical Postsynaptic membrane receives chemical

signal and membrane potential is altered - signal and membrane potential is altered - Postsynaptic AP may or may not occurPostsynaptic AP may or may not occur

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

C. Characteristics of a Chemical SynapseC. Characteristics of a Chemical Synapse– 1. One way signal conduction1. One way signal conduction– 2. Synaptic delay2. Synaptic delay– 3. Transmitter can alter the conductance of the 3. Transmitter can alter the conductance of the

postsynaptic membrane to Na+, K+, and CL-postsynaptic membrane to Na+, K+, and CL-– 4. A change in membrane conductance alters 4. A change in membrane conductance alters

membrane potentialmembrane potential– 5. Central tendency – postsynaptic nerves near 5. Central tendency – postsynaptic nerves near

the center of the axonal ending cone have a the center of the axonal ending cone have a greater chance of passing on an action greater chance of passing on an action potentialpotential

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

5. AP is NOT produced at the synapse5. AP is NOT produced at the synapse a. change in membrane potential is a. change in membrane potential is

conducted electronically (local graded conducted electronically (local graded response) across the somaresponse) across the soma

b. membrane threshold is lower at axon b. membrane threshold is lower at axon hillockhillock

c. AP will be generated IF the sum of all c. AP will be generated IF the sum of all inputs to the cell causes the membrane inputs to the cell causes the membrane potential to reach thresholdpotential to reach threshold

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

D. Synaptic TransmissionD. Synaptic Transmission– 1. Presynaptic action potential1. Presynaptic action potential

a. Effect at the bouton -a. Effect at the bouton - Opening of voltage gated Ca++ channels - Opening of voltage gated Ca++ channels - Influx of Ca++ at the axon terminalInflux of Ca++ at the axon terminal Ca++ activates calmodulin which in turn Ca++ activates calmodulin which in turn

activates a protein kinase which activates a protein kinase which phosphorylates the tethering proteins phosphorylates the tethering proteins holding the neurotransmitter vesicles holding the neurotransmitter vesicles causing releasecausing release

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

– b. Quanta release of b. Quanta release of neurotransmitterneurotransmitter 1. Each vesicle contains nearly the 1. Each vesicle contains nearly the

same number of neurotransmitterssame number of neurotransmitters 2. For each presynaptic cellular 2. For each presynaptic cellular

action potential nearly the same action potential nearly the same number of vesicles are releasednumber of vesicles are released

3. Therefore, we have about the 3. Therefore, we have about the same amount of neurotransmitter same amount of neurotransmitter released for each presynaptic released for each presynaptic action potential - action potential - Quanta ReleaseQuanta Release

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

2. Synapse2. Synapse Transmitters diffuse from the Transmitters diffuse from the

presynaptic membrane to the presynaptic membrane to the postsynaptic membrane passing postsynaptic membrane passing through the basement membrane.through the basement membrane.

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

3. Postsynaptic membrane3. Postsynaptic membrane– a. Contains receptors for the a. Contains receptors for the

neurotransmittersneurotransmitters– b. Binding of the neurotransmitter b. Binding of the neurotransmitter

causes a change in the postsynaptic causes a change in the postsynaptic membrane potential (EPSP or IPSP)membrane potential (EPSP or IPSP)

– c. No single excitatory or inhibitory c. No single excitatory or inhibitory input can bring the soma membrane input can bring the soma membrane to thresholdto threshold

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

4. Receptors4. Receptors– a. Excitationa. Excitation

1) opening of Na+ channels1) opening of Na+ channels 2) depressed conduction through 2) depressed conduction through

CL- or K+ channelsCL- or K+ channels– b. Inhibitionb. Inhibition

1) opening Cl- channels1) opening Cl- channels 2) Increased conduction through 2) Increased conduction through

K+ channelsK+ channels

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

5. Summation5. Summation– a. If the momentary sum of all of the a. If the momentary sum of all of the

EPSP bring the the axon hillock EPSP bring the the axon hillock membrane to threshold it will fire an membrane to threshold it will fire an action potentialaction potential

– b. Summation is the nerve process of b. Summation is the nerve process of integrating various inputs (decision integrating various inputs (decision making process - To fire an AP or not making process - To fire an AP or not to fire an AP)to fire an AP)

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

Summation (Cont.)Summation (Cont.)– c. Spacial summationc. Spacial summation

1) Occurs when two or more inputs arrive 1) Occurs when two or more inputs arrive simultaneouslysimultaneously

2) Two inputs are added and two EPSP 2) Two inputs are added and two EPSP inputs will depolarize the membrane twice inputs will depolarize the membrane twice as much as a single inputas much as a single input

3) one IPSP + one EPSP = zero 3) one IPSP + one EPSP = zero postsynaptic membrane changepostsynaptic membrane change

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

Summation (Cont.)Summation (Cont.)– d. Temporal summationd. Temporal summation– 1) two or more action potentials in a single 1) two or more action potentials in a single

presynaptic neuron occurring in rapid presynaptic neuron occurring in rapid succession cause the postsynaptic membrane succession cause the postsynaptic membrane to depolarize or hyperpolarize more than it to depolarize or hyperpolarize more than it would with a single inputwould with a single input

– 2) High enough excitatory presynaptic firing 2) High enough excitatory presynaptic firing rate (frequency) could cause the generation rate (frequency) could cause the generation of an action potential in the postsynaptic of an action potential in the postsynaptic nervenerve

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

Nerve to Nerve SynapseNerve to Nerve Synapse - - Nerves have thousands of other nerves Nerves have thousands of other nerves

connecting to them. The signal from any connecting to them. The signal from any one nerve generally does not generate an one nerve generally does not generate an action potential in the postsynaptic neuron action potential in the postsynaptic neuron unless the presynaptic nerve fires very unless the presynaptic nerve fires very rapidly (rapidly (Temporal SummationTemporal Summation). Normally it ). Normally it requires several nerves firing at the same requires several nerves firing at the same time to generate an action potential in the time to generate an action potential in the postsynaptic neuron (postsynaptic neuron (Spaceal SummationSpaceal Summation). ).

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

Furthermore, while some presynaptic Furthermore, while some presynaptic neurons are stimulatory others are neurons are stimulatory others are inhibitory so the end physiological inhibitory so the end physiological response in the postsynaptic neuron response in the postsynaptic neuron is determined by the relative is determined by the relative numbers of stimulatory neurons numbers of stimulatory neurons versus inhibitory neurons firing at versus inhibitory neurons firing at any one time.any one time.

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSIONChemical SynapsesChemical Synapses

NeurotransmittersNeurotransmitters

Neurotransmitters are divided into Neurotransmitters are divided into two groups depending on the rate two groups depending on the rate of actionof action– A. Small-molecule - rapidly acting A. Small-molecule - rapidly acting

transmitters (usually open ion transmitters (usually open ion channels)channels) 1. Acetylcholine1. Acetylcholine 2. Amines2. Amines 3. Amino acids3. Amino acids 4. NO4. NO

NeurotransmittersNeurotransmitters

B. Neuropeptides - action is slow B. Neuropeptides - action is slow (usually act on DNA or through (usually act on DNA or through second messenger systems) - second messenger systems) - Released in very small quantities but Released in very small quantities but effect is very potenteffect is very potent– 1. Opioids1. Opioids– 2. GI peptides2. GI peptides– 3. Hypothalamic and pituitary peptides3. Hypothalamic and pituitary peptides

NeurotransmittersNeurotransmitters

C. Fate of released neurotransmittersC. Fate of released neurotransmitters– 1. Neuropeptides - diffusion and 1. Neuropeptides - diffusion and

enzymatic hydrolysisenzymatic hydrolysis– 2. Small molecule transmitters2. Small molecule transmitters

1) diffusion1) diffusion 2) enzymatic hydrolysis2) enzymatic hydrolysis 3) re-uptake into the presynaptic 3) re-uptake into the presynaptic

terminalterminal 4) Bind to receptor than degradation 4) Bind to receptor than degradation

(enzymatic hydrolysis)(enzymatic hydrolysis)

SUMMARYSUMMARY 1. What are synapses, junctions?1. What are synapses, junctions? 2. What are the types of synapse and 2. What are the types of synapse and

how do they differ? how do they differ? 3. What is the structure of synapses?3. What is the structure of synapses? 4. What are the types of 4. What are the types of

neurotransmitters?neurotransmitters? 5. What are the possible fates of 5. What are the possible fates of

neurotransmitters?neurotransmitters?