Neural and Hormonal Communication

• The body uses neural and hormonal systems for communication.

Neural Communication

• Rapid electrical signaling describes neural communication
• Short-distance chemical transmitters are sent to nearby targets during neural communication.
• Muscles and the exocrine system are under the rapid control of neural communication.

Hormonal Communication

• Hormonal communication regulates gradual processes.
• Hormonal communication is long distance and travels via blood.
• Metabolic activities, water/electrolyte balance, and growth are regulated by hormonal communication.

Introduction to Neural Communication

• Cells have a membrane potential due to ions, proteins, etc.
• Resting Membrane Potential (RMP) is the potential in the membrane at rest.
• RMP is more negative in excitable cells.
• Rapid fluctuations occur in membrane potential in nerve and muscles cells.
• Electrical signals are produced when nerve and muscle cells are excited.
• Neurons use these signals to receive, process, initiate, and transmit messages.
• In muscles, electrical signals cause contraction
• Electrical signals are essential to the function of the nervous system and all muscles.

Introduction to Neural Communication

• Membrane potential changes include depolarization and hyperpolarization
• During depolarization less negative charge is inside.
• During hyperpolarization more negative charge is inside.
• Polarization is when the membrane potential is not 0 mV.
• Depolarization is when the potential becomes less polarized/negative than resting potential.
• Repolarization potential returns to resting potential after having been depolarized.
• Hyperpolarization is when the potential becomes more polarized/negative than resting potential.

Microelectrodes

• Microelectrodes are used for measuring electrical activity in cells, and come in a variety of styles

Cell Sizes

• Cells and components occur in a variety of sizes down to the nanometer range, necessitating several microscopy styles

Introduction to Neural Communication

• Electrical signals are produced by changes in ion movement across the plasma membrane.
• An event triggers a movement of ions.
• Net Na+ movement increases to the inside of the cell resulting in more less negative charge, resulting in depolarization.
• K+ rate increases out of the cell resulting in more negative charge inside the cell, resulting in hyperpolarization.
• Changes in membrane permeability.
• Water-soluble ions (e.g., Na+, K+) cannot cross the lipid bilayer.
• Leak channels are always open
• Gated channels (carriers) open in response to a stimulus.
• Voltage-gated channels open in response to AMP.
• Chemically gated channels open in response to chemical binding.
• Mechanically gated channels open in response to physical deformation.
• Thermally gated channels open in response to changes in temperature.

Graded Potentials

• Graded potentials are local changes in membrane potential gated channel opens.
• They occur in varying grades or degrees of magnitude or strength.
• E.g., -70 mV to -60 mV (10mV potential) or -70 mV to -50 mV (20 mV potential)
• A stronger triggering event larger resultant graded potential
• Graded potentials are spread by passive current flow.
• Current is any flow of electrical charges in a direction based on a positive charge flow.
• Resistance is when there is hindrance to electrical charge movement, V = IR
• Graded potentials die out over short distances.

Action Potentials


• Action potentials involve brief, rapid, large (100 mV) changes in membrane potential.

• Only a small portion of the membrane is affected.

• Action potentials propagate throughout the membrane.

• Action potentials do not diminish in strength.

• Potential rapidly, transiently reverses.

• The inside of the excitable cell becomes positive compared to the outside (+30 to +40 mV).

• Threshold potential: when reached, sodium channels open, depolarization happens.

Ion Movement & Action Potential

• Marked changes in membrane permeability and ion movement lead to action potential.
• Voltage-gated Nat and K+ channels are especially sensitive to voltage changes.
• K+ makes greatest contribution due to permeability.
• Changes in permeability and ion movement occur during an action potential
• Movement of Na+ and K+ with electrochemical gradient.
• Na+ entering causes more channels to open which depolarizes the space

Action Potentials

• Na+-K+ pump gradually restores concentration gradients disrupted by action potentials.

• Takes a longer time than action potential

• At the completion of an action potential, the membrane potential has been restored to resting

• Ion distribution has been altered slightly

• Only about 1 in 100,000 K+ ions present in cell leaves during action potential

• The input zone receives incoming signals from other neurons.

• The trigger zone initiates action potentials.

• The conducting zone conducts action potentials in undiminishing fashion, often over long distances.

• The axon may be from 1mm to more than 1 m long

• The output zone releases neurotransmitter that influences other cells.

• Action potentials are propagated from the axon hillock to the axon terminals

• The axon terminals release chemical messengers

Action Potentials

• Once initiated, action potentials are conducted throughout a nerve fiber
• In contiguous conduction
• And saltatory conduction.
• Contiguous Conduction involves a spread of action potential along the membrane down the length of the axon meaning that the action potential passes from one part of the axon to another in sequence
• The Refractory period ensures one-way propagation of action potentials and limits their frequency.
• Action potential cannot be initiated in a region that has just undergone an action potential. -- This leads to the abolute and relative refractory periods.
• Recently activated patch is unresponsive.

Action Potentials

• In Contiguous conduction once initiated, action potentials are conducted throughout a nerve.
• In Saltatory conduction it is we'll discuss later.
• Contiguous Conduction is Spread of action potential along the membrane down the axon, and this means on one after another, or next in sequence.
• The Refractory period ensures one-way propagation of action potentials and limits their frequency
• Action potential cannot be initiated in a region that has just undergone an action potential.
• Considering the absolute and relative refractory periods -- Not all Na+ channels are reset -- K+ channels are slow to close -- It can happen if a depolarizing event is significantly larger than the first one
• Graded potential leads to voltage > threshold causes action potential

Action Potentials

• Action-potentials exhibit all-or-none behavior.
• Stimulus strength is coded by the frequency of action potentials.
• Frequency affects how often get action potentials
• Myelination increases the conduction speed of action potentials.
• Myelination acts as an insulator, like plastic on a copper wire
• A patch of myelin can be like 300 wrapped lipid bilayers
• Results in Current jumps between nodes, producing Saltatory conduction
• Fiber diameter influences the velocity of action potential propagation
• The larger the diameter, the faster the conduction -- Larger diameter results in less current resistance
• 120 meters / sec (393 ft/s) in muscle
• 0.7 meters / sec (2.3 ft/s) in digestive tract

Synapses and Neuronal Integration

• Synapse is a junction between neurons

• In Electrical synapses, neurons are connected directly by gap junctions

• In Chemical synapses, a chemical messenger (neurotransmitter: acetylcholine, dopamine, etc.) transmits information one way across the space separating the two neurons. -- Most synapses in the human nervous system are chemical synapses

• Time associated with converting action potential to an electrical signal by chemical means takes about 0.5 to 1msec

• Neurons may terminate on: a muscle, a gland, or another neuron

• Neurons innervate a muscle or gland

Synapses and Neuronal Integration

• The Neurotransmitter carries the signal across a synapse. -->Uses Receptor channels which are combined receptor and channel units
• Some synapses excite, whereas others inhibit the postsynaptic neuron.
• This involves excitatory and inhibitory synapses due to flow of Na+ and K+
• Neurotransmitter-receptor combinations always produce the same response

Synapses and Neuronal Integration

• Neurotransmitters are quickly removed from the synaptic cleft.
• After combining, chemical transmitters are removed by diffusion, by enzymes, or are moved back into the axon by active mechanisms.
• The Grand postsynaptic potential depends on the sum of all presynaptic input activities
• Includes Temporal and spatial summation and Cancellation of concurrent EPSPs and IPSPs
• Importance of postsynaptic integration

Synapses and Neuronal Integration

• Some neurons secrete neuromodulators (serotonin) in addition to neurotransmitters.
• Chemical messengers do not cause EPSPs or IPSPs.
• This acts slowly to bring about long-term changes that subtly modulate the action of the synapse
• E.g., may influence enzymes involved with making neurotransmitters and may affect sensitivity of neuron to neurotransmitter

Synapses and Neuronal Integration

• Presynaptic inhibition means that the amount of neurotransmitter released is reduced, and Presynaptic facilitation means the neurotransmitter release is enhanced at the excitatory terminal.

Synapses and Neuronal Integration

• Drugs and diseases can modify synaptic transmission
• Most drugs that influence the nervous system function by altering synaptic mechanisms
• Neurons are linked through complex converging and diverging pathways
• Convergence is when a given neuron may have many other neurons synapsing on it
• Divergence is branching of axon terminals, so a single neuron synapses and influences many other cells

Intercellular Communication and Signal Transduction

• Communication among cells is facilitated by extracellular chemical messengers

• Can be either direct or indirect

• Direct communication involves physical contact.

• Uses gap junctions, tunneling nanotubes, and transient linkup of compatible surface markers which are like a lock and key.

• Indirect communication is the most common.

• Uses extracellular chemical messengers or signal molecules, including paracrines/autocrines, neurotransmitters, hormones and neurohormones

• A paracrine involves very short-range chemical messengers released by neurons.

• A hormone involves hormone released by endocrine glands and distributed throughout the body.

• A neurohormone involves hormone released into blood by neuron.

Intercellular Communication and Signal Transduction

• Signal Transduction involves transferring an incoming signal to target cell where it dictates cellular response and triggers the cell to do something.
• Happens by several different mechanisms.
• A Lipid soluble chemical messenger dissolves in membrane and passes through binding to Receptors inside the cell , such as cholesterol-derived steroid hormones and turning certain genes on or off.
• Receptors in plasma membrane and Triggers specific cellular activities , such as transport, secretion, activation, etc
• And proteins, neurotransmitters, etc
• A Water-soluble chemical messenger , is when the drug cannot pass through membrane.

Intercellular Communication and Signal Transduction

• Binding of a chemical messenger results in 1 of 3 responses:
• Messenger binding to a chemically gated receptor-channel opens or closes the channel
• Messenger binding to a receptor - enzyme complex activates tyrosine kinase, which phosphorylates designated that lead to the cell's response
• Messenger binding to a G-protein-coupled receptor activates a second-messenger pathway that carries out the cell's response

Tyrosine-Kinase Pathway

• Protein Kinases are enzymes that transfer phosphate groups from ATP to another protein
• Then the protein becomes activated
• In the pathway, the receptors acts as enzymes
• When a signal molecule adds P to Tyr sites
• Designated proteins then bind
• As a result, Protein is activated and triggers cell response
• Insulin uses the TK pathway to maintain glucose homeostasis

G-protein-coupled Receptor Pathway

• A Receptor is coupled to a G protein

• Binding of messenger to the receptor-channel activates the G protein

• G protein moves along membrane to an effector protein

• 2nd messanger is produced

• A chain of protein kinases are activated

• A designated protein becomes activated

Intro to Paracrine Communication

• Paracrines are either:
• Cytokines, short-range molecules regulate immune response
• Eicosanoids, short-range molecules derived from lipids
• Cytokines act locally to regulate immune responses.
• They are a collection of protein signal molecules and aresecreted by cells of the immune system and other cell types.
• They mediate inflammation and enhance activity in antibody production. Some are important to cell growth (growth factors)

Introduction to Paracrine Communication

• Eicosanoids are locally chemicals that are derived from plasma membranes.
• They are derived from fatty acid in the plasma membrane of most cell types.
• They regulate diverse processes throughout the body.
• Classes include:
• Prostaglandins
• Thromboxanes
• Leukotrienes

Introduction to Hormonal Communication

• Endocrinology:
• Study of homeostatic chemical adjustments and other activities accomplished by hormones
• Hormones are usually defined chemically as hydrophilic or lipophilic
• Secreted by endocrine glands into the blood and mechanisms of varying synthesis, storage and secretion.
• Hydrophilic hormones release through exocytosis, Hydrophobic hormones release through diffusion

Introduction to Hormonal Communication

• Hydrophilic hormones (insulin from the pancreas):
• Highly water soluble and low lipid solubility
• They dissolve in the plasma (in blood)
• Lipophilic hormones (thyroid hormone from the thyroid gland):
• High lipid solubility and poor solubility in water
• They are transported by plasma carrier proteins
• Mechanisms of synthesis, storage, secretion (by endocrine cells) vary based on the chemistry of the hormones and determine how hormones act on target cells?

Types of Hormone

• Peptide hormones are produced on ribosomes and Golgi. Packaged in the cell and secreted when needed through exocytosis only.
• Steroid hormones are derived from Cholesterol and react directly upon creation so they cannot be stored in the cell itself.
• As a result hormone can be hydrophobic or hydrophilic, and the receptors must accomodate for this as well.

Hormone action

• Effects include bind with target cell receptors
• Hydrophilic binds with receptors on plasma membrane.
• Lipophilic passes through plasma membrane and bind to receptors inside cell.
• Then alter intracellular proteins to produce an effect
• Hydrophilic activates messenger pathways inside cell.
• Lipophilic activate specific genes to form new intracellular proteins, which in turn produce an effect.

Mechanisms for Hormones: Cyclic AMP Pathway

• Hormone activates G-Protein.
• Activation causes effection of adenylate cyclase, causing the conversion of ATP into cAMP.
• cAMP serves as a protein kinase activator
• Active kinases modifies existing proteins to change in cell behavior.

G-Protein Hormone Mechanism

• G-Protein Activation causes PLC production, an effector
• Phosphodiesterase reaction with cell lipid causes DAG or IP3 production
• DAG activates kinases while IP3 liberates Calcium from lumen

Water-Soluble Hormone

• The signal from water soluble hormones must be amplified and distributed to the rest of the cell via enzymes and secondary messengers produced by enzyme activity.

Mechanisms of Action of Hydrophobic Hormones

• Steroid hormone becomes unbound from protein carrier and diffuses through the membrane.
• Hormone binds receptor in cytosol causing protein/DNA configuration change
• DNA configuration now activates, translates to mRNA, and leaves the nucleus to go to ribosome.
• Ribosome creates proteins that affect the cell.

Comparison of the Nervous System and the Endocrine Systems

• Main goal in both is regulatory systems of the body
• nervous system innervates skeletal muscles and exocrine glands and swiftly transmits electrical impulses to them
• endocrine system secretes hormones into the blood for delivery to distant sites of action
• nervous system is "wired"
• endocrine system is "wireless"

Comparison of the Nervous System and the Endocrine Systems

• Specificity:
• Neural specificity is caused by anatomic proximity -- Each neuron has a narrow range of influence (neurotransmitter)
• Endocrine specificity is caused by receptor specialization: ---Hormones go everywhere, but only work on cells with target receptors.
• Nervous and endocrine systems have their own authority, but interact functionally:. --It is intimately connected
• -Some neurons release neurohormones into blood. --Some hormones act as neuromodulators to change synaptic properties.