Group 8/26/19 Flashcards
Learning issues
Propogation of nerve impulses at the neuronal synapse [(Guyton parts of ch. 46) (Boron part of Chapter 8)]
Propogation of nerve impulses at the neuromuscular junction [(Guyton Ch. 7 finished) (Boron part of chapter 8)]
Physiology of somatic sensation of pain (receptors, types, supression)
Plan: Read Guyton-Hall ch 7 and ch 46
what are skeletal muscle fibers innervated by, and where do they come from in the spinal cord?
skeletal muscle fibers are innervated by large, myelinated nerve fibers that come from motoneurons in the anterior horns of the spinal cord
each nerve ending makes a ? with the muscle fibers near its midpoint
neuromuscular junction
motor end plate
the nerve fiber forms a complex of branching nerve terminals that invaginate into the surface of the muscle fiber but lie outside the plasma membrane, and this entire structure is the motor end plate
synaptic cleft
space between the terminal and the fiber membrane
what is acetylcholine and where is it located in the neuromuscular junction?
an excitatory transmitter that excites the muscle fiber membrane. Synthesized in cytoplasm of terminal, then absorbed into synaptic vesciles
how is acetylcholine released from its vesicles?
- voltage gated calcium channels release calcium when there is an action potential
- calcium ions activated Ca-calmodulin dependent protein kinase, phosphorylates synapsin proteins so that they release ACh vesicles
- ACh vesicles move to the active zone
- they release ACh into synaptic space via exocytosis
how is the end plate potential formed?
- there are ACh receptors in the muscle fiber membrane, which are ACh-gated ion channels
- channels opens when two ACh bind to alpha subunit proteins
- positive ions like Na, K, and Ca move through opening
- creates local positive potential in muscle fiber membrane, the end plate potential
how is acetylcholine destroyed, why is this important?
- destroyed by acetylcholinesterase, located in synaptic space, or diffuses out of synaptic space
- prevents muscle re-excitation
high safety factor
each impulse that arrives at the neuromuscular junction causes 3x as much end plate potential that was required to stimulate the muscle fiber
myasthenia gravis
a disorder that causes muscle weakness. The neuromuscular junction is unable to transmit enough signals from the nerve fibers to the muscle fibers. Autoimmune disease where the patient’s antibodies destroy their own ACh receptors. End plate potentials are too weak for depolarization.
what are some differences in muscle action potential as compared to regular action potential?
- same resting potential, -80 -90mV
- longer duration of action potential
- slower velocity of transmission
what is the importance of the transverse tubules?
- they carry action potentials and span from the outside of the cell membrane to deep in the muscle fiber.
- They run transverse to the myofibrils, and connect with the exterior of the muscle fiber.
excitatory “pulse”
when the t tubules and SR become fully excited, the calcium concentration will increase greatly, for a short period of time called a “pulse,” then the calcium pumps bring the concentration back down again.
Muscle contraction happens during the pulse
where do signals come into the neuron?
mostly dendrites, but also cell body
where do signals exit the neuron?
signals exit through one signal axon leaving the neuron, which may have branches to other parts
sensory information coming from the sensory receptors in the body goes to sensory areas in which brain structures?
spinal cord, reticular substance of medulla, pons, and mesencephalon, cerebellum, thalamus, and areas of the cerebral cortex
effectors
the muscle and glands involved in various bodily activities. Actual anatomical structures that perform functions dictated by the nerve signals.
what are the brain structures that play a role in skeletal muscle function, what does each section do?
- spinal cord, reticular substance of medulla, pons, and mesencephalon, basal ganglia, cerebellum, motor cortex
- lower regions control automatic, instantaneous muscle responses to sensory stimuli
- higher regions have deliberate complex muscle movements
integrative function of the nervous system
we receive a lot of sensory stimulation, but the processes it and channels only important sensory information to the integrative and motor regions for us to respond.
what is the role of synapses in processing information?
- determine directions that nervous signals spread
- filter passage of signals
- can amplify signals
facilitation of synapses
- each time sensory information passes through the synapse, the synapses become more capable of transmitting the same information.
- Brain will be able to generate its own signal without sensory input to trigger the same pathway as a memory, and compare new to old sensory information
functions of the spinal cord level of the CNS
- contains neuronal circuits responsible for walking and reflexes such as withdrawing from pain, standing, and bodily processes
- sends signals to control areas so that they perform their functions
structures in the lower brain/subcortical level of the CNS and their functions
- includes medulla, pons, mesencephalon, hypothalamus, thalamus, cerebellum, basal ganglia
- controls subconscious body activities, like breathing, equilibrium, eating, emotions
functions of the higher brain/cortical level of the CNS
- memory, thought processes
- works together with other areas to help them carry out their functions and its own functions
what are some differences between chemical and electrical synpases?
- chemical synapses are more common in CNS
- chemical synapse involves a neuron that secretes neurotransmitter to act on receptor proteins on membrane of next neuron
- electrical synapses involve adjacent cytoplasm of cells, connected by clusters of ion channels called gap junctions
principle of one-way conduction
chemical synapses always transmit the signal in one direction. Presynaptic neuron secretes neurotransmitter, and this goes to the postsynaptic neuron.
soma
main body of the neuron
how does the presynaptic cleft release neurotransmitters?
- presynaptic cleft contains transmitter vesicles and mitochondria
- action potential depolarized presynaptic membrane, voltage gated calcium channels open, calcium released into terminal
- calcium binds to release sites on presynaptic membrane, causes neurotransmitter to be released into cleft
what are the parts of the postsynaptic neuron membrane?
- postsynaptic neuron membrane contains receptor proteins
- receptors have a binding component (contacts synaptic cleft, binds with incoming neurotransmitter), and intracellular component (passes into postsynaptic neuron)
difference between ionotropic and metabotropic receptors?
- receptors get activated and then open ion channels in the postsynaptic cells
- ionotropic receptors directly gate ion channels
- metabotropic receptors active a second messenger that will activate substances inside the postsynaptic neuron
what are the two types of ion channels in the postsynaptic neuron membrane, and what are their roles and what are they opened by? How quickly do they act?
- cation channels, usually allow Na to pass, and excites neuron, opened by excitatory transmitters
- anion channels, usually allow Cl to pass, and inhibits the neuron, opened by inhibitory transmitters
- open and close quickly for rapid control of postsynaptic neurons
what is the benefit of a second messenger system in the postsynaptic neuron?
allow prolonged changes after transmitter gone
how does a G protein exist when it’s inactive?
inactive G protein exists in the cytosol, with GDP and alpha (activator portion), beta and gamma components
how is the G protein activated?
- receptor gets activated by neurotransmitter and undergoes conformational change to expose binding site for G protein complex
- G protein complex binds, alpha subunit releases GDP and binds to GTP, detaches from beta and gamma
- GTP-alpha complex moves in cytoplasm and carries out roles
what are some of the things a GTP-alpha complex can do?
- open specific ion channels in postsynaptic cell membrane
- activate cAMP or cGMP which play role in metabolic processes
- activate intracellular enzymes for other chemical functions
- activate gene transcription
how is a G protein inactivated?
GTP that’s bound to alpha subunit becomes GDP, so alpha dissociates
what are some ways a postsynaptic neuron can be excited?
- open Na channels to allow positive charges to flow into postsynaptic cell
- depressed conduction of Cl in or K out
- changes to the internal metabolism of the postsynaptic neuron to make it more excitable, such as increase excitatory receptors
what are some ways a postsynaptic neuron can be inhibited?
- open Cl channels to allow negative charges inside postsynaptic membrane
- increase conductance of K out of the neuron
- activation of receptor enzymes to inhibit some metabolic function, or increase inhibitory receptors
which transmitters act quickly versus slowly?
- small molecules act rapidly and cause acute responses, usually they affect conductance of ions
- neuropeptides (can be transmitters or growth factors) cause prolonged actions, long-term changes
what effect does ACh have?
usually has excitatory effect
what effect does norepinephrine have?
- control overall activity (eg wakefulness) and mood of mind
- usually excitatory effect
what effect does dopamine have?
inhibitory effect
what effect does glycine have?
inhibitory
what effect does GABA have?
inhibition
what effect does glutamate have?
excitatory
what effect does serotonin have?
inhibits pain pathways, controls mood, sleep
what effect does nitric oxide (NO) have?
- nerve terminals in areas responsible for long-term behavior and memory
- synthesized and used right away, diffuses over time
how are small-molecule, rapidly acting transmitters formed?
- synthesized in cytosol of presynaptic terminal
- absorbed by active transport into vesicles
- vesicles are continually recycled and used over and over
how are neuropeptides formed?
- synthesized as parts of protein molecules by ribosomes in the cell body
- proteins go to ER and Golgi apparatus, split, put into transmitter vesicles
- axonal streaming of axon cytoplasm brings them to nerve fiber tips
- action potentials cause vesicles to release transmitters
- vesicle autolyzed and not reused
- longer process, not as many are made but they have more potent effects
resting membrane potential of the neuronal soma
resting membrane potential of spinal motor neuron is about -65 mV
what are the ions that are important regarding the neuronal soma membrane, and where are they concentrated?
- sodium, high in ECF but low inside the neuron
- potassium, high inside the neuron, low in the ECF
- chloride, high in the ECF, low inside the neuron
Nernst potential and equation
a potential that exactly opposes the movement of an ion, gives the potential inside the membrane. Negative for positive ions, and positive for negative ions
EMF (mV) = +/-61 x log (concentration inside/concentration outside)
how is the postsynaptic membrane affected by synaptic excitation?
- excitatory transmitter acts on membrane excitatory receptor to increase membrane’s permeability to Na+
- Na+ rushes into cell, potential increases to -45mV, called the excitatory postsyanptic potential (EPSP)
- increase in potential caused by simultaneous discharge of many terminals in succession, summation
where is the action potential triggered in the postsynaptic neuron and where does it go?
- eventually EPSP high enough to trigger action potential
- action potential begins in the initial segment of the axon where axon leaves the soma; initial segment membrane has many voltage-gated Na channels
- travels along the axon and also backward to soma and dendrites
how do inhibitory synapses affect the postsynaptic membrane?
- inhibitory synapses open mainly chloride channels, into the cell
- K channels open and K moves to exterior
- Both movements contribute to hyperpolarization
- increase in negativity beyond normal resting membrane potential is the inhibitory postsynaptic potential (IPSP)
presynaptic inhibition
- an inhibitory substance (usually GABA) is released onto the outside of the presynaptic nerve fibrils
- opens ion channels, Cl diffuses into terminal fibril, and prevents synaptic transmission
spatial summation in neurons
- excitation of a single presynaptic terminal rarely excites the neuron
- many presynaptic terminals over a wide area of neuronal membrane are stimulated at the same time, and their effects are added together in spatial summation
- EPSP large enough to reach the threshold for firing
temporal summation in neurons
successive discharges from a single presynaptic terminal can occur rapidly and add onto each other to create greater postsynaptic potential
simultaneous summation of inhibitory and excitatory postsynaptic potentials
simultaneous trigger of IPSP and EPSP in the membrane potential can nullify each other completely or partially
facilitation of neurons
a postsynaptic potential may not rise high enough to reach the threshold for firing, so another excitatory signal entering the neuron can excite the neuron more easily
what kind of signals can dendrites transmit?
- Dendrites can’t transmit action potentials well due to not enough channels and high thresholds for excitation.
- They can transmit electrotonic current instead, spread of electrical current by ion conduction.
decremental conduction
- dendrite ends may have high levels of EPSPs, but a lot of it is lost before reaches soma
- long dendrites with thin membrane are leaky to electric currents
- there’s a decrease in membrane potential as it spreads electrotonically along dendrite toward soma, greater effect for dendrites far away
excitatory vs inhibitory state in neuron
neuron that has higher degree of excitation is in excitatory state; higher degree of inhibition means in inhibitory state
fatigue of synaptic transmission
- when excitatory synapses are repetitively stimulated at rapid rate, the number of discharges by the postsynaptic neuron is at first very great, but then it becomes progressively less
- due to exhaustion/partial exhaustion of the transmitter stores in presynaptic terminals, inactivated postsynaptic membrane receptors, and abnormal ion concentrations in postsynaptic cell
effect of pH of surrounding interstitial fluids on synaptic transmission
- alkalosis normally greatly increases neuronal excitability
- acidosis greatly depresses neuronal activity
effect of hypoxia on synaptic transmission
cessation of oxygen can cause inexcitability in neurons
strychnine
- drug agent that increases excitability of neurons, by inhibiting the action of some normally inhibitory transmitter substances
- Excitatory effects are more pronounced, neurons rapidly give repetitive discharge, tonic muscle spasms
how do anesthetics affect synaptic transmission
- increase neuronal membrane threshold for excitation, decrease synaptic transmission
- most lipid soluble and may change physical characteristics of neuronal membrane so less sensitive to excitatory agents
why is there a synaptic delay?
- discharging the transmitter substance by the presynaptic terminal
- diffusing transmitter to postsynaptic neuronal membrane
- action of transmitter on membrane receptor
- action of receptor to raise membrane permeability
- inward diffusion of sodium to raise EPSP to high enough level to trigger action potential
where is acetylcholine synthesized?*
basal nucleus of Meynert
where is dopamine synthesized?*
ventral tegmentum, SNc (Substantia nigra pars compacta)
where is GABA synthesized?*
nucleus accumbens
where is norepinephrine synthesized?*
locus ceruleus
where is serotonin synthesized?*
raphe nucleus
