Human Physiology
Resting Membrane Potential (-70mv)
All cells under resting conditions have a potential difference across their plasma membranes, with the inside of the cell negatively charged with respect to the outside
Postsynaptic Neuron
A neuron conducting signals away from a synapse
Presynaptic Neuron
A neuron that conducts a signal toward the synapse
describe the various postsynaptic mechanisms of varying synaptic effectiveness.
A. immediate past history of electrical state of postsynaptic membrane B. effects of other neurotransmitters or neuromodulators acting on postsynaptic neuron C. Up or down regulation and desensitization of receptors D. certain drugs and diseases
explain why action potentials are said to be "all-or-none.
Action potentials either occur maximally or they do not occur at all
Which of the major positive ions is found in the extracellular fluid but not in the intracellular fluid
Ca2+
initially, compartment 1 contains 0.15 M Nacl, compartment 2 contains 0.15 M KCl, and no ion movement occurs because the ion channels are closed.
Potassium ions- if these K+ channels are opened, K+ will diffuse down its concentration gradient from compartment 2 into compartment 1. Sodium ions will not be able to move across the membrane. After a few potassium ions have moved into compartment 1, the compartment will have an excess of positive charges, leaving behind an excess of negative charge in compartment 2. Sodium ions- Na+ ions will initially move from compartment 1 to compartment 2. when compartment 2 is positive with respect to compartment 1, the difference in electrical charge across the membrane will begin to drive Na+ ions from compartment 2 back to compartment 1 and, eventually, net movement of Na+ will cease
Neuron
The basic unit of the nervous system is the individual nerve cell. neurons operate by generating electrical signals that move from one part of the cell to another part of the same cell or to neighboring cells
Polarize
The resting membrane potential, at -70 mV, is polarized. meaning that the outside and inside of a cell have different net charge
Within the fluid compartment, what is the total charge
Zero
Repolarizing
depolarized returns toward the resting value
Leak K+ channels
potassium channels that are open when a membrane is a rest
Electrical Potential
separated electrical charges of opposite sign have potential to do work if they are allowed to come together. - or because it is determined by the difference in the amount of charge between two points-- potential difference
list the five major classes (including miscellaneous!) of neurotransmitters and neuromodulators
1. Acetylcholine (ACh) 2. Biogenic amines catecholamines dopamine norepinephrine epinephrine serotonin (5-hydroxytryptamine, 5-HT) Histamien 3. Amino Acids Excitatory amino acids; for example, glutamate inhibitory amino acids; for example, gamma-aminobutyric acid (GABA) and glycine 4. Neuropeptides for example, endogenous opioids, oxytocin, tachykinins 5. Gases for example, nitric oxide, carbon monoxide, hydrogen sulfide 6. purines for example, adenosine and ATP
Identify the three functional classes of neurons: afferent, efferent, and interneurons
1. Afferent Neurons A. Transmit information into the central nervous system from receptors at their peripheral endings B. Cell body and the long peripheral process of the axon are in the peripheral nervous system; only the short central process of the axon enters the central nervous system. 2. Efferent Neurons A. Transmit information out of the central nervous system to effector cells, particularly muscles, glands, or other neurons B. Cell body, dendrites, and small segment of the axon are in the central nervous system; most of the axon is in the peripheral nervous system Interneurons A. Function as integrators and signal changers B. integrate groups of afferent and efferent neurons into reflux circuits C. Lie entirely within the central nervous system D. Account for > 99 percent of all neurons
Action Potential
1. All-or-none. once membrane is depolarized to threshold, amplitude is independent of the size of the initiating event. 2. cannot be summed 3. has a threshold that is usually about 15 mv depolarized relative to the resting potential 4. has a refractory period 5. is conducted without decrement; the depolarization is amplified to a constant value at each point along the membrane 6. duration is constant for a given cell type under constant conditions 7. is only a depolarization 8. initiated by a graded potential 9. mechanism depends on voltage-gate channels
describe how the magnitude of the graded potential is affected by the magnitude of the stimulus, the distance the potential has traveled
1. Because the electrical signal decreases with distance, graded potentials ( and the local current they generate) can function as signals only over short distances (a few millimeters)
define and give three examples of graded potentials.
1. Graded potential- membrane potential change of variable amplitude and duration that is conducted decrementally; has no threshold or refractory period 2. Receptor potential- A graded potential produced at the peripheral endings of afferent neurons (or in separate receptor cells) in response to a stimulus 3. Pacemaker potential- A spontaneously occurring graded potential change that occurs in certain specialized cells 4. Synaptic potential- a graded potential change produced in the postsynaptic neuron in response to the release of a neurotransmitter by a presynaptic terminal; it may be depolarizing (an excitatory postsynaptic potential or EPSP) or hyperpolarizing (an inhibitory postsynaptic potential or IPSP)
discuss the importance of ligand-gated channels and mechanically-gated channels to the initiation of an action potential and the importance of voltage-gated channels to the excitability of the membrane.
1. Ligand-gated channels- open in response to the binding of signaling molecules 2. mechanically-gated channels- open in response to physical deformation (stretching) of the plasma membranes 3. Whereas these types of channels often serve as the initial stimulus for an action potential, voltage-gated channels give a membrane the ability to undergo action potentials
recognize that at the resting membrane potential, the driving force for sodium diffusion is much greater than that for potassium.
1. Na+/K+- ATPase Pump-actually move three sodium ions out of the cell for every two potassium ions that they bring in. This unequal transport of positive ions makes the inside of the cell more negative than it would be from ion diffusion alone.
understand why the resting membrane potential of cells is much closer to the equilibrium potential for potassium than to the equilibrium potential for sodium.
1. The concentration gradients determine their equilibrium potentials, and the relative permeability determines how strongly the resting membrane potential is influenced toward those potentials 2. resting potential is generated across the plasma membrane largely because of the movement of K+ out of the cells down its concentration gradient through open K+ channels
distinguish between the afferent and efferent divisions of the peripheral nervous system.
1. afferent neurons are sometimes called primary afferents or first-order neurons because they are the first cells entering the central nervous system in the synaptically linked chains of neurons that handle incoming information 2.efferent neurons carry signals out from the central nervous system to muscles or glands
Graded potentials
1. amplitude varies with size of the initiating event 2. can be summed 3. has no threshold 4. has no refractory period 5. is conducted decremental; that is, amplitude decreases with distance 6. can be a depolarization or a hyper polarization 7. initiated by environment stimulus (receptor), by neurotransmitter (synapse), or spontaneously 8. mechanism depends on ligand-gated channels or other chemical or physical changes
describe the components of the central and peripheral nervous systems.
1. central- spinal cord lies within the bony vertebral column 2. peripheral nervous sytem transmit signals between the central nervous system and receptors and effectors in all other part of the body.
The magnitude of the resting membrane potential depends mainly on two factors
1. differences in specific ion concentrations in the intracellular and extracellular fluids 2. differences in membrane permeabilities to the different ions, which reflect the number of open channels for the different ions in the plasma membrane
describe the synthetic pathway for the catecholamines and how and where they are metabolized. Understand why fibers that secrete norepinephrine as a neurotransmitter are called adrenergic. Know the two major classes of adrenergic receptors.
1. dopamine, norepinephrine (NE), and Epinephrine all contain a catechol ring (a six-carbon ring with two adjacent hydroxyl groups) and an amine group; thus, they are called catecholamines. 2. synthesis of catecholamines begins with the uptake of tyrosine by the axon terminal and its conversion to another precursor, L-dihydroxy-phenylalanine (L-dopa) by the rate-limiting enzyme in the pathway, tyrosine hydroxylase 3. catoecholamine neurotransmitters are also broken down in both the extracellular fluid and the axon terminal by enzymes such as monoamine oxidase secretions of the adrenal gland "adrenaline" the adjective "adrenergic" is commonly used to describe neurons that release norepinephrine or epinephrine and also describe the receptors to which those chemical binds 4. two major classes alpha-adrenergic receptors- exist in two subclasses, a1 and a2 they act presynaptically to inhibit norepinephrine relase or postsynaptically to either stimulate or inhibit activity at different types of K+ channels beta-adrenergic receptors- act via stimulatory G proteins to increase cAMP in the postsynaptic cell
Convergence
1. hundreds or thousands of synapses from many different presynaptic cells can affect a single postsynaptic cell 2. convergences allows information from many sources to influence a cell's activity
describe how local current surrounding the depolarized region produces depolarization of adjacent regions.
1. local current moves positive charges toward the depolarization site along the outside of the membrane and away from the depolarization site along the inside of the membrane.
discuss the importance of the Na+/K+-ATPase to maintaining the concentration gradients for sodium and potassium and the membrane potential
1. maintains the concentration at stable levels 2. helps establish the membrane potential directly
discuss how the synthesis of neuropeptide neurotransmitters differs from that of other types of neurotransmitters
1. neurotransmitters, which are synthesized in the axon terminals by very few enzyme-mediated steps. The neuropeptides, in contrast are derived from large precursor proteins, which themselves have little, if any, inherent biological activity. The synthesis of precursors, directed by mRNA, occurs on ribosomes, which exist only in the cell body and large dendrites of the neuron, often a considerable distance from axon terminals or varicosities where the peptides are released
describe the general ways in which neurotransmitters can directly or indirectly affection channels on the postsynaptic membrane.
1. once neurotransmitters are released from the presynaptic axon terminal, they diffuse across the cleft 2.unbound neurotransmitters are removed from the synaptic cleft when they are actively transported back into the presynaptic axon terminal (in the process called reuptake) or, in some cases, into nearby glial cells; diffuse away from the receptor site; or are enzymatically transformed into inactive substances, some of which are transported back into the axon terminal for reuse
recognize that autonomic efferents consist of two neurons: a preganglionic and postganglionic neuron.
1. preganglionic neurons- the neurons passing between the central nervous system and the ganglia 2. postganglionic neurons- those passing between the ganglia and the effector cell
describe the general functions/actions of the biogenic amine serotonin and the amino acid neurotransmitters glutamate, aspartate, GABA, and glycine.
1. serotonin (5-hydroxytryptamine, or 5-HT)- it is produced from tryptophan, an essential amino acid. in general, serotonin has an excitatory effect of pathways that are involved in the control of muscles, and an inhibitory effect on pathways that mediate sensation 2. glutamate- This mechanisms couples frequent activity across a synapse with lasting changes in the strength signaling across the synapse and is thus to be a cellular process underlying learning and memory 3. Aspartate- an excitatory neurotransmitter in CNS; ionized form of the amino acid aspartic acid 4. GABA- an amino acid neurotransmitter commonly occurring at inhibitory synapses in the central nervous system 5. glycine- major neurotransmitter released from inhibitory interneurons in the spinal cord and brainstem. it bind to ionotropic receptors on postsynaptic cells that allow Cl- to enter, thus preventing them for approaching the threshold for firing action potentials
understand how spatial and temporal summation interact to activate a postsynaptic cell to threshold.
1. temporal summation- because the input signals arrive from the same presynaptic cell a different times 2. spatial summation- because the two inputs occurred at different locations on the same cell. 3. the interaction of multiple EPSPs through spatial and temporal summation can increase the inward flow of positive ions and bring the postsynaptic membrane to threshold so that action potentials are initiated
discuss how the gases nitric oxide and carbon monoxide can act as neurotransmitters
1. they are produced by enzymes in axon terminals (in response to Ca 2+ entry) and simply diffuse from their sites of origin in one cell into the intracellular fluid of other neurons or effector cells, where they bind to and activate proteins. 2. nitric oxide- released from neurons activates guanylyl cyclase in recipient cells, which increases concentration of the second messenger cyclic GMP
distinguish between an excitatory postsynaptic potential and an inhibitory postsynaptic potential and discuss which ions are typically responsible for each.
1.Excitatory postsynaptic potential- depolarizing graded potential in postsynaptic neuron in response to activation of excitatory synapse --both electrical and concentration gradients drive Na+ into the cell, whereas for K+, the electrical gradient opposes the concentration gradient. potassium ions out of the cell and larger number of sodium ions into the cell 2. inhibitory postsynaptic potential- activation of an inhibitory synapses lessens likelihood that the postsynaptic cell will depolarize to threshold and generate an action potential -- at an inhibitory synapse, the activated receptors on the postsynaptic membrane open Cl- or K+ channels; Na+ permeability is not affected
Identify the major positive and negative ions in the intracellular and extracellular
1.Extracellular- Na+ and Cl- concentrations are lower inside the cell than outside 2. Intracellular- K+ concentrations is greater inside the cell
Divergence
1.single presynaptic cell can send branches to affect many other postsynaptic cells 2. allows one information source to affect multiple pathways
describe the mechanism of ion-channel changes that generate and terminate action potentials. Appreciate that the action potential is a good example of a physiologically important positive-feedback mechanism.
A. APs occur in excitable membranes because these membranes contain many voltage-gated Na+ channels. these channels open as the membrane depolarizes, causing a positive feedback opening of more voltage-gated Na+ channels and moving the membrane potential toward the Na+ equilibrium potential B. The Action potential ends as the Na+ channels inactivate and K+ channels open, restoring resting conditions
Presynaptic Factors
A. Availability of neurotransmitter 1. availability of precursor molecules 2. amount of the rate-limiting enzyme in the pathway for neurotransmitter synthesis B. axon terminal membrane potential C. Axon terminal Ca 2+ D activation of membrane receptors on presynaptic terminal 1. axo-axonic synapses 2. autoreceptors 3. other receptors E. certain drugs and diseases, which act via the above mechanism A-D
Resting Membrane Potential
A. Na+/K+- ATPase pump establishes concentration gradients and generates a small negative potential B. Greater net movement of K+ than Na+ makes the membrane potential more negative on the inside C. At a steady negative resting membrane potential, ion fluxes through the channels and pump balance each other
describe how and where acetylcholine is synthesized and metabolized. Discuss what is meant by cholinergic fibers and nicotinic and muscarinic receptors.
Acetylcholine- is a major neurotransmitter is the peripheral nervous system at the neuromuscular junction and in the brain. neurons that release ACh are called Cholinergic neurons -- Acetylcholine is synthesized from choline and acetyl coenzyme A in the cytoplasm of synaptic terminals and stored in synaptic vesicles. Metabolized by Acetylcholinesterase. this enzyme is located on the presynaptic and postsynaptic membranes and rapidly destroys ACh, releasing choline and acetate nicotinic- acetylcholine receptor that responds to nicotine; primarily, receptors at motor end plate and on postganglionic autonomic neurons muscarinic receptor- acetylcholine receptor that responds to the mushroom poison muscarine; located on smooth muscle, cardiac muscle, some CNS neurons, and glands
describe an action potential and identify the types of cells with excitable membranes capable of generating action potentials
Action Potential- A brief all-or-none depolarization of the membrane, which reverses polarity in neurons; it has a threshold and refractory period and is conducted without decrement - Neurons and muscle cells, as well as some endocrine, immune, and reproductive cells, have plasma membranes capable of producing action potentials - these membranes are called excitable membranes, and their ability to generate action potential is known as excitability
Nerves
Groups of afferent and efferent neurons, together with connective tissue and blood vessels, form the nerves of the peripheral nervous system. 1. is a bundle of axons (fiber) bound together by connective tissue
recognize that the efferent division is divided into the somatic and autonomic nervous systems and that the autonomic division is divided into the parasympathetic and sympathetic divisions.
Somatic 1. consists of a single neuron between central nervous system and skeletal muscle cells 2. innervates skeletal muscle 3. can lead only to muscle excitation Autonomic 1. has two-neuron chain (connected by a synapse) between central nervous system and effector organ 2. innervates smooth and cardiac muscle, glands, and GI neurons 3. can be either excitatory or inhibitory
Synapse
The anatomically specialized junction between two neurons where one neuron alters the electrical and chemical activity of another
Depolarized
When its potential becomes less negative (closer to zero) than the resting level.
autoreceptors
a receptor on a cell affected by chemical messenger released from the same cell
describe the mechanism by which action potentials are propagated. Differentiate between action potential propagation in myelinated axons and in unmyelinated axons.
action potentials appear to jump from one node to the next as they propagate along a myelinated fiber; for this reason, such propagation is called saltatory conduction. Propagation via saltatory conduction is faster than propagation in nonmyelinated fibers of the same axon diameter. this sections of the membrane, more charge arrives at the node adjacent to the active node, and an action potential is generated there sooner than if the myelin were not present.
Excitatory synapse
brings the membrane of the postsynaptic cell closer to threshold
discuss the role of calcium in stimulating exocytosis of synaptic vesicles.
calcium ions activate processes that lead to the fusion of docked vesicles with the synaptic terminal membrane
Describe how positive and negative charges interact with each other
charges of the same type repel each other- positive charge repels positive charge, and negative charge repels negative charge. in contrast, oppositely charged substances attract each other and will move toward each other if not separated by some barrier
Neurotransmitter
chemical messenger used by neurons to communicate with each other or with effectors
Central Nervous System
composed of the brain and spinal cord
Peripheral Nervous System
consisting of the nerves that connect the brain or spinal cord with the body's muscles glands, and sense organs.
define the absolute period Understand the ionic basis of these periods
during the action potential, a second stimulus, no matter how strong, will not produce a second action potential -- this occurs during the period when the voltage-gated Na+ channels are either already open or have proceeded to the inactivated state during the first action potential
define equilibrium potential as the membrane potential needed to oppose the diffusion of ions based upon a given concentration gradient. Recognize that each ion species has its own equilibrium potential
equilibrium potential- membrane potential at which these two fluxes become equal in magnitude but opposite in direction. - equilibrium potential for one ion species can be different in magnitude and direction from those for other ion species, depending on the concentration gradients between the intracellular and extracellular compartments for each ion
define relative refractory periods. Understand the ionic basis of these periods
following the absolute refractory period, there is an interval during which a second action potential can be produced, but only if the stimulus strength is considerably greater than usual. -- during the relative refractory period, some but not all of the voltage gated Na+ channels have returned to a resting state and some of the K+ channels that repolarized the membrane are still open
Inhibitory synapse
hyperpolarizes the postsynaptic cell or stabilizes it at its resting levels
Summation
if additional stimuli occur before the graded potential has died away, these can be added to the depolarization from the first stimulus. (important with sensation)
differentiate between neurotransmitters and neuromodulators. Appreciate the complexity of communication in the nervous system without becoming overwhelmed by it.
in general, neurotransmitters cause EPSPs and IPSPs, and neuromodulators cause, via second messengers, more complex metabolic effects in the postsynaptic cell -- the action of neurotransmitters are usually faster than those of neuromodulators -- a substance can act as a neurotransmitter at one type of receptor and as a neuromodulator at another
recognize that the membrane potential of a postsynaptic cell reflects the effects of possibly hundreds of different synaptic inputs, both excitatory and inhibitory.
intracellular recording from a postsynaptic cell during times of excitatory synaptic activity when the cell is depolarized, and inhibitory synaptic activity when the membrane hyperpolarizes
discuss how the functional anatomy of a synapse can account for the one-way conduction of action potentials in a neural circuit.
one-way conduction across synapses causes action potentials to transmit along a given multi neuronal pathway in one direction
list the ways that action potentials can be initiated physiologically
receptor potential pacemaker potential synaptic potential
Overshoots
refers to a reversal of the membrane potential polarity that is, when the inside of a cell becomes positive relative to the outside.
Nerve fibers
refers to a single axon
chemical synapse
signals are transmitted across the synaptic cleft by means of chemical messenger- a neurotransmitter- released from the presynaptic axon terminal. -in general, the neurotransmitter is stored on the presynaptic side of the synaptic cleft, whereas receptors of the neurotransmitters are on the postsynaptic side. therefore, most chemical synapse operate in only one direction
compare and contrast the sympathetic and parasympathetic divisions of the autonomic nervous system. State the differences in neurotransmitter used, differences in anatomy, and functional differences. Appreciate the importance of dual innervation of organs to allow for fine-tuned control of organ function (akin to having both an accelerator and a brake).
sympathetic division is also called the thoracolumbar division parasympathetic division is called the craniosacral division -- parasympathetic division, acetylcholine is also a neurotransmitter between the postganglionic neuron and the effector cell. in the sympathetic division, norepinephrine is usually the transmitter between the postganglionic neuron and the effector cell
Decremtental
that is, the flow of charge decreases at the distance from the site of origin of the graded potential increases
understand how current, voltage, and resistance are related (ohm's law) I= V/R
the effect of voltage V and resistance R on Current I is expressed. -materials that have a high electrical resistance reduce current flow and are known as insulators. - materials that have a low resistance allow rapid current flow and are called conductors
electrical synapses
the plasma membrane of the presynaptic and postsynaptic cells are joined by gap junctions. these allow the local currents resulting from arriving action potentials to flow directly across the junction through the connecting channels from one neuron to the other. this depolarizes the membrane of the second neuron to threshold, continuing the propagation of the action potential. communication between cells via electrical synapse is extremely rapid
explain why the threshold potential must be reached in order for a neuron to generate an action potential.
the rate at which the membrane depolarizes to threshold determines the action potential frequency
Electrogenic pump
when a pump moves net charge across the membrane and contributes directly to the membrane potential,
Hyperpolarized
when the potential is more negative than the resting level