7. Intercellular Communication Types

Intercellular Communication

• Involves a continuous process
• Essential for maintaining homeostasis
• Necessary for coordinating processes that enable an organism's growth, development, division, and cellular organization into tissues
• Cells send signals through exocytosis or gradient diffusion, and receive them via specific receptors on their surface or internally

Types of Intercellular Communication

• Gap junctions
• Autocrine
• Paracrine
• Endocrine
• Synapse

Gap Junctions

• Enable propagation of electrical activity and direct transport of chemical substances (up to MW 500) between adjacent cells
• Help orchestrate the functions of neighboring cells
• GJs close in the event of damage to a cell, isolating it from healthy tissue
• Opening and closing is regulated by IC Ca2+, phosphorylation, pH, and voltage

Autocrine Communication

• Cells release chemical signals that bind to their own receptors, thereby affecting cellular functions
• Some tumor cells secrete growth factors and express receptors for them, creating positive feedback
• Platelet activation by ATP and ADP stored in dense granules is an example of a physiological function

Paracrine Communication

• Cells release chemical signals that diffuse through the extracellular fluid to neighboring cells
• Endothelial cells secrete factors affecting vascular smooth muscle (endothelin, NO) and angiogenesis
• Spermatogenesis takes place in seminiferous tubules under the paracrine influence of Sertoli cells

Endocrine Communication

• An endocrine cell releases a chemical signal into the blood to transport it to more or less-distant target tissues equipped with specific receptors
• Signaling occurs over long distances, but it is slower and more diffuse than neuronal communication
• Endocrine cells, not necessarily glands, produce hormones (first messengers)
• Target tissue responses are relatively slow but long-lasting
• Hormones regulate reproduction, growth, and metabolism

Synapse Communication

• Communication is fast and well-targeted
• Synapses are connections between neurons, or between neurons and other cells like neuromuscular junctions
• Specialized synapses have postsynaptic membranes equipped with receptors for specific neurotransmitters
• Target tissue reactions are relatively fast and do not last long

Synapse Classification

According to the type of signal transmission

• Electrical
• Chemical

According to elements in contact

• Axo-dendritic synapse: axon connects to another neuron's dendrites
• Axo-axonic synapse: axon connects to another neuron's axon
• Axo-somatic synapse: axon connects to another neuron's cell body

According to function

• Excitatory
• Inhibitory

Charles Scott Sherrington (1857-1952)

• Coined the term synapse for connection between neurons

Specialized Synapse Types

• Between sensory neuron and sensor
• Between motor neuron and muscle (motor end-plate)
• Between neuron and secretory cell
• Between neuron and ECF

Structure of Synapse

• Presynaptic neuron
• Synaptic cleft
• Postsynaptic neuron

Electrical Synapse

• First described in the nervous system of lobster
• In humans, electrical synapses enable electrical synchronization of many neurons
• Extracellular space is reduced to approximately 2 nm
• Cytoplasms are continuous
• Information is carried by ions via gap junctions with minimum synaptic delay
• The flow of information is bidirectional

Chemical Synapse

• The predominant type of synapse
• Transmission of impulses between the pre- and postsynaptic neuron is chemical, via neurotransmitter release from the presynaptic neuron
• AP running on the axolemma of the presynaptic neuron causes exocytosis of neurotransmitter
• Neurotransmitter diffuses across the synaptic cleft and binds to receptors on the subsynaptic membrane
• This leads to a series of changes that generate a postsynaptic AP

Chemical Synapse Elements

Presynaptic element (synaptic button)

• Ending of the axon
• Contains synaptic vesicles which contain neurotransmitter and mitochondria, responsible for the high synthesis activity in the button

Presynaptic membrane

• Without myelin sheath on the nerve terminal
• Excitable membrane replaced by non-excitable membrane

Synaptic cleft

• Space filled with extracellular fluid, 10-50 nm

Postsynaptic element

• Neuronal dendrite, cell body/axon, or effector cells (muscle, gland)

Postsynaptic membrane

• Plasmalemma of the postsynaptic element

Subsynaptic membrane

• Faces the presynaptic membrane
• Non-excitable and contains receptors

Characteristics of Synaptic Transmission

• Transmission is unidirectional, from presynaptic element to postsynaptic element
• Synapses determine the direction of nerve impulse propagation
• Synaptic delay is the time interval between AP arrival on the presynaptic nerve ending and response generation in the postsynaptic neuron, about ~0.5 ms
• Neurotransmitter release is the slowest step

Neurotransmitter Removal Methods

• Enzymatic degradation, such as acetylcholine
• Reuptake of neurotransmitter into the presynaptic element
• Diffusion into surrounding extracellular space
• Uptake into postsynaptic element and subsequent degradation

Process of a Chemical Synapse

• AP on the presynaptic neuron's membrane causes depolarization of the synaptic button
• Opening of voltage-gated Ca2+ channels occurs
• Ca2+ enters Intracellular Fluid (ICF), increasing the IC Ca2+ concentration
• Synaptic vesicles move toward the membrane
• Neurotransmitter is released via fusion
• Neurotransmitter diffuses across the synaptic cleft following its concentration gradient
• Neurotransmitter binds to the receptor
• Generation of either an excitatory postsynaptic potential (EPSP) or an inhibitory postsynaptic potential (IPSP) results

Postsynaptic Potential

• Binding of neurotransmitter to its receptor causes the opening or closure of relevant channels
• This leads to a change in the membrane potential of the postsynaptic membrane
• This process may reach a threshold, leading to a new AP
• The response is electrotonic, local, and graded
• Can be either an excitatory postsynaptic potential (EPSP) or an inhibitory postsynaptic potential (IPSP)

EPSP

• Depolarization
• Increased permeability to Na+
• Increased probability of AP generation
• Excitatory synapse

IPSP

• Hyperpolarization
• Increased permeability to K+
• Decreased probability of AP generation
• Inhibitory synapse

Chemical Synapse Regulation of Transmission

• One neuron in the CNS has thousands of afferent synaptic contacts, some inhibitory and some excitatory
• A new AP on the postsynaptic neuron is only possible if the threshold for AP is reached on the axon hillock
• Many EPSPs should be generated on the postsynaptic membrane by incoming impulses through summation

Summation

Spatial Summation

• Several presynaptic neurons create synapses on a single postsynaptic neuron → Simultaneous release of neurotransmitter from many presynaptic neurons → The postsynaptic neuron is affected by sufficient neurotransmitter to reach the threshold → EPSP → postsynaptic AP

Temporal Summation

• High frequency of AP on the presynaptic neuron → Release of neurotransmitter exceeds its degradation → Accumulation of neurotransmitter in the synaptic cleft → Threshold EPSP → postsynaptic AP
• Exception: In the motor end-plate, one presynaptic AP leads to one postsynaptic AP

Neurotransmitters

• Catecholamines
• Acetylcholine
• Serotonin
• y-aminobutyric acid
• Glutamic acid
• Glycine

Postulated Criteria to Define Neurotransmitters

• Specific localization in neuronal synaptic vesicles
• Specific biosynthesis
• Release by exocytosis
• Binding to specific receptors
• Inactivation by synaptic enzymes
• Simulation of the drug effect by its administration

Revised Criteria for Neurotransmitters (2003)

• Synthesis and storage in the presynaptic neuron
• Presynaptic stimulation must lead to substance release
• Substance application must evoke the same response as presynaptic stimulation
• Agents blocking postsynaptic response to pre-synaptic stimulation must also block the response induced by exogenous administration of the substance
• Postsynaptic response should be short and well-defined
• Tested substance must have the same pharmacological characteristics as the endogenous neurotransmitter

Types of Neurotransmitters

• Low molecular-weight neurotransmitters and neuromodulators
• Purines
• Peptides

NORADRENALINE

• CNS: ~18,000 neurons in the locus coeruleus regulate arousal, sleep-wake cycle, attention, memory, emotions, behavioral flexibility, inhibition, and stress
• PNS: Present in postganglionic sympathetic fibers
• Adrenal medulla

Catecholamines

• Dopamine
• Noradrenaline
• Adrenaline

Acetylcholine

• CNS: Meynert nucleus, reticular formation, basal ganglia etc.
• PNS: Preganglionic sympathetic/parasympathetic fibers, postganglionic parasympathetic fibers, some postganglionic sympathetic fibers (sweat glands), somatic motor neurons

Dopamine

• Dopaminergic nuclei contain ≈400,000 neurons
• Projects to the hypothalamus, basal ganglia, prefrontal cortex, and hippocampus
• Functions in motivation, reward, fear, and prolactin secretion
• Receptors: D1-D5
• Degeneration leads to Parkinson's disease

Serotonin

• Found in a few brainstem nuclei-raphe nuclei
• Projects to the spinal cord to modulate pain
• Projects to the medulla and pons
• Forms part of the ascending reticular activating system (RAAS)

Y-Aminobutyric Acid (GABA)

• Predominant inhibitory amino acid in the CNS
• ≈25-45% of synapses in the central nervous system of vertebrates are GABAergic
• Involved in neuronal hyperpolarization
• Found in the brainstem and forebrain
• Synthesized from glutamate

Glutamic Acid

• Principal excitatory neurotransmitter in the CNS
• Glu receptors are widely distributed in the reticular formation of the brainstem
• Primary neurotransmitter of RAAS
• Glutamatergic neurons form synapses in thalamus and cortex

Glycine

• Inhibitory neurotransmitter in the CNS, particularly in the spinal cord, brainstem, and retina
• Ionotropic receptors are coupled to Cl- channels, causing hyperpolarization
• Serves as a neurotransmitter for inhibitory interneurons
• Inhibited by strychnine
• Leads to uncoordinated spreading of irritation