Block Exam #2

Endocrine Signaling

1. Hormones
2. Long distance
3. Long time scale (minutes, hours, days)

Neuronal Signaling

1. Close proximity
2. Very fast (ms)

Nervous System

1. Two regions


1. Central nervous system (CNS)
2. Peripheral nervous system (PNS)

Central nervous system (CNS)

1. Includes


1. Brain
2. Spinal cord

Peripheral nervous system (PNS)

1. Includes


1. Nerves leaving from CNS


1. Cranial, thoracic, lumbar, sacral

Cell Groups

1. Two cell groups


1. Neurons
2. Glial cells (neuroglia)

Neurons

1. Cell group
2. Conduct electrical signals but generally can not divide
3. Respond to chemical and physical stimuli
4. Conduct electrochemical impulses (rapid change in charge)
5. Release chemical regulators


1. Neurotransmitters (ligands)
6. Enable perception of sensory stimuli, learning, memory, control muscle contraction, and regulate glands

Neuron Cells (neuronal)

1. Chemical from another cell
2. Electrical within the same cell
3. Chemical to another cell

Neuron Structure

1. Cell body


1. Contains nucleus and other organelles
2. Cluster in groups called nuclei in CNS/ganglia in PNS
2. Dendrites


1. Receive chemical signals
2. Conduct a graded impulse toward the cell body
3. Axon


1. Conducts action potentials away from cell body towards terminal

Classification of Neurons and Nerves

1. Based on direction impulses are conducted
2. Two types


1. Sensory neurons
2. Motor neurons

Sensory Neurons

1. Conduct impulses from sensory receptors to CNS
2. To the brain


1. Afferent

Motor Neurons

1. Conduct impulses from CNS to target organs (muscles or glands
2. From the brain


1. Efferent
3. Two main classes


1. Somatic
2. Autonomic

Somatic Motor Neurons (LMNs)

1. Responsible for


1. Reflexes
2. Voluntary control of skeletal muscles
2. Selective
3. Have


1. Cell bodies in the **CNS**
2. **One** neuron traveling from spinal cord to effector muscle cell
4. Fast conduction speed


1. Myelinated
2. Large diameter

Autonomic Motor Neurons

Responsible for


1. Innervating involuntary targets/organs


1. Smooth muscle of visceral organs and blood vessels, airways, cardiac muscle, and glands


1. Automatic
2. Homeostasis is a dynamic balance between autonomic branches


1. Sympathetic (Fight/flight)
2. Parasympathetic (Rest/digest)
3. Has **two** neurons in **PNS**


1. 1st has cell bodies in brain or spinal cord and synapses in an autonomic ganglion in PNS
2. 2nd has cell bodies in ganglion and synapses on effector cell
4. Release mainly acetylcholine and norepinephrine


1. May be excitatory (stimulate) or inhibitory


1. Effect on target cell depends upon what ion channel the receptor for the neurotransmitter is coupled to


1. Neurotransmitter communication more universal
2. Target cells (the type of ion channel) makes the response specific

Sympathetic

1. Autonomic motor neuron
2. Emergency situations
3. “Fight or flight”


1. Activity/exercise
4. Location of nerve


1. Thoracic/Lumbar
5. Short axon of ganglia
6. Functions


1. Release of norepinephrine from postganglionic neurons
2. Secretion of epinephrine from adrenal medulla
3. Prepares body for intense physical activity in emergencies


1. Increasing heart rate, diverting blood to skeletal muscles, dilating bronchioles for increased O2
4. Tunes down “housekeeping” organs


1. Constricts blood vessels to those organs

Parasympathetic

1. Autonomic motor neuron
2. Normal functions
3. “Rest and digest”


1. Housekeeping
4. Location of nerve


1. Cranial/Sacral
5. Long axon of ganglia
6. Functions


1. Antagonistic to sympathetic division
2. Release of **ACh** from postganglionic neurons
3. Slows heart rate, increases digestive activities, increases blood flow to “housekeeping” organs
4. Constricts blood vessels to skeletal muscles diverting some blood away from skeletal muscles to “housekeeping” organs

Neuroglia (Glial Cells)

1. Cells that are non-conducting but support neurons
2. Two types found in the PNS
3. Four types are found in the CNS

Schwann Cells

1. Neuroglia (Glial Cells)
2. Found in PNS
3. Form myelin sheaths around axons of PNS neurons

Satellite Cells

1. Neuroglia (Glial Cells)
2. Found in PNS
3. Support cell bodies of neurons in PNS

Oligodendrocytes

1. Neuroglia (Glial Cells)
2. Found in CNS
3. Form myelin sheaths around axons of CNS neurons

Microglia

1. Neuroglia (Glial Cells)
2. Found in CNS
3. Migrate around CNS tissue
4. Phagocytize foreign and degenerated material

Astrocytes

1. Neuroglia (Glial Cells)
2. Found in CNS
3. Regulate external environment of neurons
4. Thought to help form synapses
5. Secrete regulatory molecules that support tight junctions between cells that line blood vessels in brain


1. Blood brain barrier

Ependymal Cells

1. Neuroglia (Glial Cells)
2. Found in CNS
3. Line ventricles
4. Secrete cerebrospinal fluid

Blood-Brain Barrier

1. Capillaries in brain do not have pores between adjacent \n cells but are joined by tight junctions


1. Not a leaky filter
2. Substances only moved by selective processes of diffusion through endothelial cells, active transport, and bulk transport
3. Movement is transcellular through cell membrane


1. Not paracellular (between the cells)
4. Astrocytes


1. Secrete regulatory molecules that support tight junctions between cells that line blood vessels in brain

Membrane Potential (Charge)

1. Resting Membrane Potential
2. Changes in Potential


1. Graded potentials


1. Small local signal
2. Action potentials


1. Large electrical signal sent down axon

Causes of Resting Membrane Potential (RMP)

1. Na/K ATPase Pump


1. Maintains gradient
2. Electrogenic
2. Concentration gradients for K+ and Na+
3. Movement of K+ down its concentration gradient
4. Very little K+ flux is needed to generate a membrane potential
5. Some K+ Leak

Ion Concentration: ICF vs. ECF

1. Intracellular fluid (ICF)
2. Extracellular fluid (ECF)

Intracellular fluid (ICF)

1. Cytosol within the cell
2. K+ accumulates at high concentrations in cell


1. Na+/K+ pumps actively bring K+ into the cell
2. Negative anions inside cell attract cations


1. Anions are proteins made by cell

Extracellular fluid (ECF)

1. Surrounds the cells
2. Serves as a circulating reservoir
3. Na+ accumulates at high concentrations outside of cell because
4. Na+/K+ pumps actively take Na+ out of the cell

Potential Difference

1. When there is a different charge on each side of the plasma membrane
2. Inside of the cell is more negative than the outside
3. Due to


1. Action of Na+/K+ pumps
2. Negatively charged molecules inside the cell
3. Permeability of the membrane at rest to K+


1. K+ leaky channels open at rest
4. Impermeability to Na+

Resting Membrane Potential

1. Membrane potential of a cell not producing any impulses
2. Depends on


1. Ratio of concentrations of each ion on either side of membrane
2. Specific permeability to each ion
3. K+, Na+, Ca2+ and Cl− contribute to resting potential, but because membrane is most permeable to K+ at rest, it has the greatest influence
4. A change in concentration of any ion inside or outside the cell can change the resting potential
5. Resting membrane potential is between -65mV and -85mV


1. Neurons are usually at −70mV
6. A change in the permeability of the membrane for any ion will change the membrane potential

Depolarization

1. Occurs when positive ions enter the cell (usually Na+)
2. (Less -) of the cell is excitatory

Hyperpolarization

1. Occurs when positive ions leave the cell (usually K+) or negative ions (Cl−) enter the cell
2. (More -) is inhibitory

Ligand Gated Channel

1. A receptor and a channel
2. Located on dendrites and cell bodies of neurons
3. Allow a few ions in each time

Voltage Gated Channel

1. A channel that opens at a specific voltage


1. Membrane potential
2. Located at nerve terminal
3. Allow lots of ions in at once

Graded Potentials

1. Potential magnitude and change in charge is based on stimulus size


1. Variable
2. Amount of ligand
2. Potential decreases w/ distance from origin
3. Change in membrane potential can summate by multiple channel openings
4. Small, localized signal
5. Summation of small signals leads to a bigger change in membrane potential
6. Can be depolarizing or hyperpolarizing depending on what ion(s) is moving
7. Summation of depolarizing potential activates neuron

Voltage-Gated Na+ Channels

1. At resting membrane potential (-70mV)


1. Closed


1. Active = closed
2. Inactive = open
2. At action potential threshold (-55mV)


1. Open


1. Active = open
2. Inactive = open


1. Depolarizes to -55mV


1. Sodium rushes into cell
2. Membrane potential rises
3. At refractory period (+30mV)


1. Inactive


1. Active = open
2. Inactive = closed


1. Inactivated at +30mV

TTX

1. Tetrodotoxin
2. Local anaethestics


1. Lidocaine, novocaine, xylocaine
3. Block the channel so no AP sent down axon
4. No “pain” signal reaches brain

Voltage-Gated K+ Channels

1. At resting membrane potential (-70mV)


1. Closed
2. At action potential threshold (-55mV)


1. Closed during depolarization
3. +30mV


1. Open
2. K+ rushes out of the cell and begins repolarization
4. Relative refractory period


1. Open
2. A very strong stimulus can overcome this

Action Potential

1. Large, rapid reversal of membrane potential in a region of a cell that allow electrical impulse to be carried over long distances


1. Sending the signal
2. Action potential magnitudes are constant
3. Three phases of the action potential


1. Depolarization
2. Repolarizaton
3. Hyperpolarization

Depolarization

1. Phase of action potential
2. Membrane potential difference gets smaller


1. Threshold (-55mV) to +30mV

Repolarization

1. Phase of action potential
2. Membrane potential returns to resting membrane potential


1. +30mV to -70mV

Hyperpolarization

1. Phase of action potential
2. Membrane potential difference gets larger


1. -70mV to something more negative
2. Something more negative back to -70mV

Refractory Periods

1. When the membrane can’t respond or is less sensitive to depolarizing stimuli
2. Two types


1. Absolute refractory period
2. Relative refractory period
3. Action potentials can only go one-way = down the axon
4. There is a refractory period after each action potential when that part of neuron cannot become excited again
5. Each action potential remains a separate, all-or-none event

Absolute Refractory Period

1. Occurs during the action potential
2. No action potential capability
3. Na+ voltage-gated channels


1. Inactive


1. Active = open
2. Inactive = closed

Relative Refractory Period

1. Increased stimulus strength needed to produce an action potential because membrane potential is hyperpolarized
2. K+ channels are still open

All-or-None

1. Once threshold has been reached, an action potential will happen
2. Size of stimulus will not affect the size of action potential


1. Always will reach +30mV
3. More stimulus at cell body can make action potentials occur more frequently

Conduction of Nerve Impulses

1. ONE WAY
2. When an action potential occurs at given point on neuron membrane, voltage-gated Na+ channels open as \n a wave down length of axon
3. Action potential at one location serves as depolarization stimulus for next region of axon
4. Area that just was activated is in absolute refractory so it can’t be activated again from this action potential
5. Only after the absolute refractory period is over, can a NEW stimulus cause another AP in that region

Conduction Rate

1. Can be affected by two factors


1. Myelination
2. Diameter
2. Diameter of axon


1. Increased diameter of neuron reduces resistance to the spread of charges
3. Examples


1. Thin, unmyelinated neuron speed = 1.0m/sec
2. Thick, myelinated neuron speed = 100m/sec (faster)

Unmyelinated Axons

1. Action potentials are produced down entire length of axon at every patch of membrane
2. Conduction rate = slow


1. So many action potentials are generated and each one is an individual event
3. Amplitude of each action potential is the same

Myelinated Axons

1. Myelin provides insulation, improving speed
2. Nodes of Ranvier allow Na+ and K+ to cross the membrane every 1−2 mm
3. Na+ ion channels are concentrated at the nodes
4. Action potentials “leap” from node to node


1. Saltatory conduction
5. Schwann cells


1. Form myelin sheaths around peripheral axons
6. Oligodendrocytes


1. Form myelin sheaths around the axons of CNS neurons

Synapse

1. Functional connection between a neuron terminal and \n the target cell
2. CNS


1. Second cell will be another neuron
3. PNS


1. Second cell could be a neuron, muscle or gland
4. If one neuron is signaling another neuron, first is called presynaptic, and second is called postsynaptic


1. Presynaptic neuron can signal the dendrite, cell body, or axon of a second neuron
5. Synapses can be electrical or chemical

Neuromuscular Junction

1. Synapse that occurs in the PNS
2. A nerve to muscle connection
3. Consists of axon terminals, motor end plates on the muscle membrane, and Schwann cell sheaths
4. Somatic motor neuron branches at its distal end
5. The motor end plate is a region of muscle membrane that contains high concentrations of ACh receptors
6. An action potential arrives at the axon terminal, causing voltage-gated Ca2+ channels to open
7. Calcium entry causes synaptic vesicles to fuse with presynaptic membrane
8. Release ACh into synaptic cleft
9. Acetylcholine (ACh) is metabolized by acetylcholinesterase (AChE)

Electrical Synapse

1. Occur in smooth muscle and cardiac muscle, between some neurons of brain, and between glial cells


1. Cells are joined directly together by gap junctions in membranes
2. Requires direct contact

Chemical Synapse

1. Most synapses involve the release of a chemical called a \n neurotransmitter from axon terminal
2. The synaptic cleft is very small


1. Released neurotransmitter can readily diffuse across
3. Does NOT require direct contact


1. For cell-to-cell communication when cell membranes are NOT directly connected

Release of Neurotransmitter

1. Neurotransmitter is enclosed in synaptic vesicles in axon terminal
2. Each neuron can only make/release 1 type of neurotransmitter
3. Neurons are often named by the NT that they make
4. When the action potential reaches end of axon, voltage-gated Ca2+ channels in terminal open
5. Intracellular Ca2+ stimulates fusing of synaptic vesicles to plasma membrane for exocytosis of neurotransmitter

Sequence to Release Neurotransmitter

1. Action potential reaches axon or nerve terminal
2. Voltage-gated Ca2+ channels open
3. Ca2+ binds to sensor protein in cytoplasm
4. Ca2+ protein triggers vesicles to fuse with membrane
5. Ca2+ protein complex stimulates exocytosis of neurotransmitter


1. NT released
2. NT diffuses across synapse
3. NT binds to ligand gated channel and signals cell

Actions of Neurotransmitters

1. Neurotransmitter diffuses across synapse, where it binds to specific receptor protein


1. Neurotransmitter is referred to as chemical ligand
2. This results in the opening of ligand-gated ion channels on the next cell
3. The effect on next cell can be an inhibitory (hyperpolarizing) or excitatory (depolarizing) graded potential depending on whether the ligand gated channel allows K+, Cl-, or Na+ ions to flow

Removal of Neurotransmitter

1. Two ways


1. Reuptake by transporter on presynaptic terminal (recycled)
2. Enzymatic digestion on the postsynaptic side (degraded)
2. Some might diffuse out of cleft

Acetylcholine (ACh)

1. Neurotransmitter
2. Directly opens ligand-gated channels when it binds to its receptor
3. Excitatory from all somatic motor neurons to skeletal muscle cells (and some areas of CNS)


1. Ach Receptor is a Na+ channel
4. Excitatory or Inhibitory in autonomic motor neurons


1. Effect is determined by what ion channel is coupled to the Ach receptor


1. K+ or Cl- = inhibit/hyperpolarize
2. Na+ or Ca2+ = activates/depolarizes
5. **Cholinergic**


1. ACh is used by all preganglionic neurons (sympathetic and parasympathetic)
2. Released from most parasympathetic postganglionic neurons
3. Some sympathetic postganglionic neurons (those that innervate sweat glands/skeletal muscle blood vessels) release ACh.

Acetylcholine Receptors

1. Two kinds


1. Nicotinic ACh receptors
2. Muscarinic ACh receptors

Nicotinic ACh Receptors

1. Can be stimulated by nicotine
2. Located on


1. Motor end plate of skeletal muscle cells
2. Autonomic ganglia
3. Some parts of CNS

Muscarinic ACh Receptors

1. Can be stimulated by muscarine (from mushrooms)
2. Located in


1. CNS
2. Membrane of smooth and cardiac muscles
3. Glands innervated by autonomic motor neurons

Acetylcholinesterase (AChE)

1. Enzyme that inhibits/inactivates/degrades ACh in synapse
2. Located on target cell membrane
3. Hydrolyzes ACh into acetate and choline, which are taken back into presynaptic cell for reuse

Serotonin

1. Monoamine


1. Regulatory molecules derived from amino acids
2. Derived from L-tryptophan

Histamine

1. Monoamine


1. Regulatory molecules derived from amino acids
2. Derived from histidine

Catecholamines

1. Monoamine


1. Regulatory molecules derived from amino acids
2. Derived from tyrosine
3. Include


1. Dopamine
2. Norepinephrine
3. Epinephrine


1. Norepinephrine and epinephrine = “adrenaline”

Monoamine Action and Inactivation

1. Monoamines are made in presynaptic axon, released via exocytosis, diffuse across the synapse, and bind to specific receptors
2. They are quickly taken back into presynaptic cell (reuptake) via transporters and either repackaged or \\n degraded by monoamine oxidase (MAO)
3. MAO inhibiters (MAOI’s) are a common class of therapeutic drugs to slow breakdown of monoamine NTs so the effects of released monoamines increases

Monoamine Action and Inactivation Steps

1. Monoamine produced and stored in synaptic vesicles
2. Action potentials open gated Ca2+ channels, leading to release of neurotransmitter
3. Neurotransmitters enter synaptic cleft
4. Re uptake of most neurotransmitter from synaptic cleft
5. Inactivation of most neurotransmitter by MAO

Cell to Cell Communication

1. Via neurons to target cell
2. Very fast signal sent to target cell


1. Must be in close proximity

Muscle

1. Three types


1. Smooth
2. Cardiac
3. Skeletal
2. Muscle is a key target of neurons

Muscle Cell

1. Muscle fiber
2. Myofiber

Cell Membrane

1. Sarcolemma


1. Sarco = of the muscle

Cytoplasm

1. Sarcoplasm


1. Sarco = of the muscle

Modified Endoplasmic Reticulum

1. Sarcoplasmic Reticulum


1. Sarco = of the muscle
2. AKA S.R.


1. Ca2+

Skeletal Muscle

1. Fibers are large, multinucleate cells
2. Striated or striped
3. Voluntary
4. NO GAP JUNCTIONS
5. Individual fibers can be selectively activated
6. Large range of force
7. Can sustain contraction

Cardiac Muscle

1. Fibers are smaller than skeletal muscle, branched, and uninucleate (one nucleus)
2. Cells are joined in series by junctions called intercalated disks
3. Striated, sarcomeres, involuntary
4. Action potentials are longer so only twitch contractions
5. Contraction is due to myosin/actin cross bridges stimulated by calcium
6. Regulated by autonomic nervous system
7. Cells electrically linked via gap junctions (all cells linked will contract together as a unit)
8. Some cells exhibit pacemaker potentials
9. Under sympathetic and parasympathetic control as well as hormone control
10. Contraction via sliding filaments
11. Cardiac myocytes contract as a unit and heart functions as a pump


1. Cycles of contraction and relaxation

Smooth Muscle

1. Fibers are small
2. Non striated
3. Involuntary
4. No sarcomeres
5. Contraction is due to myosin/actin cross bridges stimulated by calcium


1. Contract as a unit to change lumen diameter
6. Slow, sustained contractions


1. Regulated by autonomic nervous system
2. Located in


1. Blood vessel walls and bronchioles (tubes that constrict due to contraction to change flow)
2. Digestive organs, urinary & reproductive tracts, produce peristaltic waves to propel contents of these organs
3. Still contain large amounts of actin/myosin
4. Long actin filaments attached to dense bodies
5. Myosin filaments are stacked vertically and can form cross bridges with actin its entire length
6. Arrangement allows contraction even when greatly stretched

Skeletal Muscle Fiber

1. A muscle is made of many muscle cells
2. Myofiber = single cell, containing multiple bundles of contractile elements
3. Major elements of a myofiber


1. Myofibrils = Sarcomeres, contractile units, thick and thin filaments
2. Mitochondria = ATP generation
3. Sarcoplasmic reticulum = Ca2+ storage
4. T-tubules
4. In somatic motor neuron


1. If no action potential = skeletal muscle off
2. If action potential = skeletal muscle on

Excitation-Contraction Coupling: Skeletal Muscle

1. Steps of connecting an action potential to muscle contraction
2. In the somatic motor neuron


1. ACh released
3. In the sarcolemma


1. ACh binds to nicotinic ACh receptors
2. Opens ligand (chemically) gated channels
3. Na+ diffuses in producing depolarizing stimulus
4. Action potential produced
4. In the transverse tubules


1. Action potentials conducted along transverse tubules
2. Action potentials open voltage-gated Ca2+ channels
5. In the sarcoplasmic reticulum


1. Ca2+ release channels in SR open
2. Ca2+ diffuses out into sarcoplasm
6. In the myofibrils


1. Ca2+ binds to troponin
2. Stimulates contraction

T-Tubules

1. Extensions of cell membrane (sarcolemma) that associate w/ ends (terminal cisternae) of sarcoplasmic reticulum
2. Steps


1. T-tubule brings action potentials into interior of muscle fiber
2. Sarcoplasmic reticulum stores Ca2+

Calcium

1. Sarcoplasmic reticulum is modified endoplasmic reticulum that stores Ca2+ when muscle is at rest
2. Upon AP stimulation, Ca2+ diffuses out of calcium release channels (ryanodine receptors)
3. At end of contraction, Ca2+ is actively pumped back into sarcoplasmic reticulum


1. SERCA atpase pump
4. Ca2+ goes back to its source
5. In skeletal muscle, ALL Ca2+ comes from sarcoplasmic reticulum

Thick and Thin Filaments

1. Sarcomere
2. A bands


1. Thick filament + thin filament overlap
2. Thick filament = MYOSIN
3. Z discs (lines)


1. Center of each I band
4. H bands


1. Center of A band
2. No thin filament overlap
5. I bands


1. Only thin filaments
2. Primarily ACTIN

Thick and Thin Filaments cont…

1. Sarcomere
2. M-line


1. Protein filaments anchoring thick filaments
3. Titin


1. Sets resting sarcomere length
2. Runs from Z disc to M line

Contraction

1. Cross bridge heads bind thin filament and pull inward


1. Thin filaments slide inward along thick filaments
2. Sliding Filament Mechanism


1. When a muscle contracts, sarcomeres \n shorten


1. A bands do not shorten, but move closer together
2. I bands shorten, but thin filaments do not
3. Thin filaments slide inward toward H band
4. H band shortens or disappears

Myosin

1. Thick filament
2. Aggregates of myosin with a long fibrous “tail” \n connected to globular “head”
3. Globular head has


1. Actin-binding site
2. ATP-binding site
3. Hinge on which it can pivot
4. ATPase activity
4. Myosin cross-bridge head is the “working” part

Myosin ATPase

1. Globular head of myosin binds ATP and splits off \n its terminal phosphate
2. ATP = ADP + Pi


1. Activates globular myosin head, causing it to pivot
3. Ready to work: pull actin

Thin Filaments

1. 3 main protein groups


1. Actin polymers
2. Regulatory proteins


1. Troponin
2. Tropomyosin
2. At rest (relaxed)


1. Regulatory proteins prevent interaction between actin and myosin
3. In the resting state, myosin binding sites on actin are BLOCKED by tropomyosin
4. Troponin holds tropomyosin in place


1. Prevents myosin (crossbridge) heads from binding

Actin Polymers

1. Thin filament
2. Made of 300-400 G-actin subunits in double row
3. Twisted to form helix

Contraction 1

1. Ca2+ released into cytosol
2. Calcium binds to troponin
3. Troponin moves tropomyosin away from myosin-binding site
4. Thin Filament activation by Ca2+

Contraction 2

1. Thick filament
2. Hydrolysis of bound ATP allows binding of head to actin
3. “Energizes” the head (like cocking a trigger)
4. Release of Pi pulls the trigger producing a powerstroke
5. Pulls thin filament towards center

Contraction 3

1. After power stroke, ADP is released
2. New ATP binds
3. Makes myosin release actin
4. Cycle begins again, continuing until the sarcomere has shortened

Contraction 4

1. Myosin is energized but thin filament binding blocked
2. Contraction is dependent on CALCIUM activating the thin filament to allow myosin to bind actin

Contraction Summary

Cross-bridges bind actin causing sarcomere shortening and force production

Cross-Bridge Cycle

Thick-filament focus

Excitation-Contraction Coupling Sequence: Skeletal

Steps of connecting an action potential to muscle contraction


1. Somatic motor neuron releases ACh a neuromuscular junction
2. Net entry of Na+ through ACh receptor-channel initiates a muscle action potential
3. Action potential in t-tubule alters conformation of DHP receptor
4. DHP receptor opens RyR Ca2+ release channels in sarcoplasmic reticulum, and Ca2+ enters cytoplasm
5. Ca2+ binds to troponin, allowing actin-myosin binding
6. Myosin heads execute power stroke
7. Actin filament slides toward center of sarcomere
8. Sarcoplasmic Ca2+ATPase pumps Ca2 back into SR
9. Decrease in free cytosolic \[Ca2+\] causes Ca2+ to unbind \n from troponin
10. Tropomyosin re-covers binding site
11. When myosin heads release, elastic elements pull filaments back to their relaxed position

SERCA Pumps

1. Pumps Ca2+ back into SR via ATP hydrolysis
2. For relaxation of muscles

Muscle Relaxation

1. Action potentials stop; no further calcium release from sarcoplasmic reticulum
2. Active pumping of Ca2+ back into sarcoplasmic reticulum via SERCA pump (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase; requires ATP)
3. ATP is required for both initiation and termination of contraction


1. Unbinding of myosin head from actin at the end of a cross-bridge cycle/Energization (activation) of myosin head
2. Pumping of Ca2+ out of sarcoplasm back into sarcoplasmic reticulum

Sequence of Muscle Contraction (Simple Skeletal)

1. Acetylcholine from motor neuron
2. Ach binds N. AchR and Na+ comes into cell
3. Action potentials (propagated down T-tubules)
4. Opening of calcium release channels (ryanodine receptor) in SR
5. Calcium released, binds to troponin
6. Contraction

Sequence of Muscle Relaxation (Simple Skeletal)

1. Action potentials cease
2. Calcium release channels close
3. Ca2+ATPase pumps (SERCA) move Ca2+ back into SR
4. No more Ca2+ bound to troponin
5. Tropomyosin blocks myosin binding sites on actin