Events in Muscle Contraction - the sequence of events in crossbridge formation:

1) In response to Ca²⁺ release into the sarcoplasm, the troponin-tropomyosin complex removes its block from actin, and the myosin heads immediately bind to active sites.

2) The myosin heads then swivel, the Working Stroke, pulling the Z-lines closer together and shortening the sarcomeres. As this occurs the products of ATP hydrolysis, ADP and Pi, are released.

3) ATP is taken up by the myosin heads as the crossbridges detach. If ATP is unavailable at this point the crossbridges cannot detach and release. Such a condition occurs in rigor mortis, the tensing seen in muscles after death, and in extreme forms of contracture in which muscle metabolism can no longer provide ATP.

4) ATP is hydrolyzed and the energy transferred to the myosin heads as they cock and reset for the next stimulus.

Excitation-Contraction Coupling: the Neuromuscular Junction  

Each muscle cell is stimulated by a motor neuron axon. The point where the axon terminus contacts the sarcolemma is at a synapse called the neuromuscular junction. The terminus of the axon at the sarcolemma is called the motor end plate. The sarcolemma is polarized, in part due to the unequal distribution of ions due to the Sodium/Potassium Pump.

1) Impulse arrives at the motor end plate (axon terminus) causing  Ca²⁺ to enter the axon.

2) Ca²⁺ binds to ACh vesicles causing them to release the ACh (acetylcholine) into the synapse by exocytosis. 

3) ACH diffuses across the synapse to bind to receptors on the sarcolemma. Binding of ACH to the receptors opens chemically-gated ion channels causing Na⁺ to enter the cell producing depolarization.

4) When threshold depolarization occurs, a new impulse (action potential) is produced that will move along the sarcolemma. (This occurs because voltage-gated ion channels open as a result of the depolarization -

5) The sarcolemma repolarizes:

a) K⁺ leaves cell (potassium channels open as sodium channels close) returning positive ions to the outside of the sarcolemma. (More K⁺ actually leaves than necessary and the membrane is hyperpolarized briefly. This causes the relative refractory period) (b) Na⁺/K⁺ pump eventually restores resting ion distribution.  The  Na⁺/K⁺ pump is very slow compared to the movement of ions through the ion gates. But a muscle can be stimulated thousands of times before the ion distribution is substantially affected.

6) ACH broken down by ACH-E (a.k.a. ACHase, cholinesterase). This permits the receptors to respond to another stimulus. 

Excitation-Contraction Coupling:

1) The impulse (action potential) travels along the sarcolemma. At each point the voltaged-gated Na+ channels open to cause depolarization, and then the K+ channels open to produce repolarization.

2) The impulse enters the cell through the T-tublules, located at each Z-disk, and reach the sarcoplasmic reticulum (SR), stimulating it.

3) The SR releases Ca²⁺ into the sarcoplasm, triggering the muscle contraction as previously discussed. 

4) Ca²⁺ is pumped out of the sarcoplasm by the SR and another stimulus will be required to continue the muscle contraction.

Functional Divisions of the Nervous System:

1) The Voluntary Nervous System - (ie. somatic division) control of willful control of effectors (skeletal muscles) and conscious perception. Mediates voluntary reflexes.

2) The Autonomic Nervous System - control of autonomic effectors - smooth muscles, cardiac muscle, glands. Responsible for "visceral" reflexes

Carbohydrates:

• about 3% of the dry mass of a typical cell
• composed of carbon, hydrogen, & oxygen atoms (e.g., glucose is C₆H₁₂O₆)
• an important source of energy for cells
• types include:
  • monosaccharide (e.g., glucose) - most contain 5 or 6 carbon atoms
  • disaccharides
    • 2 monosaccharides linked together
    • Examples include sucrose (a common plant disaccharide is composed of the monosaccharides glucose and fructose) & lactose (or milk sugar; a disaccharide composed of glucose and the monosaccharide galactose)
  • polysaccharides
    • several monosaccharides linked together

Examples include starch (a common plant polysaccharide made up of many glucose molecules) and glycogen (commonly stored in the liver)

Neurophysiology

Transmission of an action potential. This occurs in two ways:

1) across the synapse - synaptic transmission. This is a chemical process, the result of a chemical neurotransmitter.

2) along the axon - membrane transmission. This is the propagation of the action potential itself along the membrane of the axon.

Synaptic transmission - What you learned about the neuromuscular junction is mostly applicable here as well. The major differences in our current discussion are:

1) Transmission across the synapse does not necessarily result in an action potential. Instead, small local potentials are produced which must add together in summation to produce an action potential.

2) Although ACh is a common neurotransmitter, there are many others and the exact effect at the synapse depends on the neurotransmitter involved.

3) Neurotransmitters can be excitatory or inhibitory. The result might be to turn off the next neuron rather than to produce an action potential

The basic steps of synaptic transmission are the same as described at the neuromuscular junction

1) Impulse arrives at the axon terminus causing opening of Ca²⁺ channels and allows Ca²⁺  to enter the axon. The calcium ions are in the extracellular fluid, pumped there much like sodium is pumped. Calcium is just an intermediate in both neuromuscular and synaptic transmission.

2) Ca²⁺  causes vesicles containing neurotransmitter to release the chemical into the synapse by exocytosis across the pre-synaptic membrane.

3) The neurotransmitter binds to the post-synaptic receptors. These receptors are linked to chemically gated ion channels and these channels may open or close as a result of binding to the receptors to cause a graded potential which can be either depolarization, or hyperpolarization depending on the transmitter. Depolarization results from opening of Na⁺ gates and is called an EPSP. Hyperpolarization could result from opening of K⁺ gates and is called IPSP. 

4) Graded potentials spread and overlap and can summate to produce a threshold depolarization and an action potential when they stimulate voltage gated ion channels in the neuron's trigger region.

5) The neurotransmitter is broken down or removed from the synapse in order for the receptors to receive the next stimulus. As we learned there are enzymes for some neurotransmitters such as the Ach-E which breaks down acetylcholine. Monoamine oxidase (MAO) is an enzyme which breaks down the catecholamines (epinephrine, nor-epinephrine, dopamine) and nor-epinephrine (which is an important autonomic neurotransmitter) is removed by the axon as well in a process known as reuptake. Other transmitters may just diffuse away.

Graded Potentials - these are small, local depolarizations or hyperpolarizations which can spread and summate to produce a threshold depolarization. Small because they are less than that needed for threshold in the case of the depolarizing variety. Local means they only spread a few mm on the membrane and decline in intensity with increased distance from the point of the stimulus. The depolarizations are called EPSPs, excitatory post-synaptic potentials, because they tend to lead to an action potential which excites or turns the post-synaptic neuron on. Hyperpolarizations are called IPSPs, inhibitory post-synaptic potentials, because they tend to inhibit an action potential and thus turn the neuron off.

Summation - the EPSPs and IPSPs will add together to produce a net depolarization (or hyperpolarization).

Temporal summation- this is analogous to the frequency (wave, tetany) summation discussed for muscle. Many EPSPs occurring in a short period of time (e.g. with high frequency) can summate to produce threshold depolarization. This occurs when high intensity stimulus results in a high frequency of EPSPs.

Spatial summation - this is analogous to quantal summation in a muscle. It means that there are many stimuli occurring simultaneously. Their depolarizations spread and overlap and can build on one another to sum and produce threshold depolarization.

Inhibition - When the brain causes an IPSP in advance of a reflex pathway being stimulated, it reduces the likelihood of the reflex occurring by increasing the depolarization required. The pathway can still work, but only with more than the usual number or degree of stimulation. We inhibit reflexes when allowing ourselves to be given an injection or blood test for instance.

Facilitation - When the brain causes an EPSP in advance of a reflex pathway being stimulated, it makes the reflex more likely to occur, requiring less additional stimulation. When we anticipate a stimulus we often facilitate the reflex.

Learned Reflexes - Many athletic and other routine activities involve learned reflexes. These are reflex pathways facilitated by the brain. We learn the pathways by performing them over and over again and they become facilitated. This is how we can perfect our athletic performance, but only if we learn and practice them correctly. It is difficult to "unlearn" improper techniques once they are established reflexes. Like "riding a bike" they may stay with you for your entire life!

Post-tetanic potentiation - This occurs when we perform a rote task or other repetitive action. At first we may be clumsy at it, but after continuous use (post-tetanic) we become more efficient at it (potentiation). These actions may eventually become learned reflexes

The Action Potential

The trigger region of a neuron is the region where the voltage gated channels begin. When summation results in threshold depolarization in the trigger region of a neuron, an action potential is produced. There are both sodium and potassium channels. Each sodium channel has an activation gate and an inactivation gate, while potassium channels have only one gate. 

A) At the resting state the sodium activation gates are closed, sodium inactivation gates are open, and potassium gates are closed. Resting membrane potential is at around -70 mv inside the cell. 

B) Depolarizing phase: The action potential begins with the activation gates of the sodium channels opening, allowing Na+ ions to enter the cell and causing a sudden depolarization which leads to the spike of the action potential. Excess Na+ ions enter the cell causing reversal of potential becoming briefly more positive on the inside of the cell membrane.

C) Repolarizing phase: The sodium inactivation gates close and potassium gates open. This causes Na+ ions to stop entering the cell and  K+ ions  to leave the cell, causing repolarization. Until the membrane is repolarized it cannot be stimulated, called the absolute refractory period.

D) Excess potassium leaves the cell causing a brief hyperpolarization. Sodium activation gates close and potassium gates begin closing. The sodium-potassium pump begins to re-establish the resting membrane potential. During hyperpolarization the membrane can be stimulated but only with a greater than normal depolarization, the relative refractory period.

Action potentials are self-propagated, and once started the action potential progresses along the axon membrane. It is all-or-none, that is there are not different degrees of action potentials. You either have one or you don't.

Functions of the nervous system:

1) Integration of body processes

2) Control of voluntary effectors (skeletal muscles), and mediation of voluntary reflexes.

3) Control of involuntary effectors (  smooth muscle, cardiac muscle, glands) and mediation of autonomic reflexes (heart rate, blood pressure, glandular secretion, etc.)

4) Response to stimuli

5) Responsible for conscious thought and perception, emotions, personality, the mind.

Membrane Potential

• Membrane potentials will occur across cell membranes if
  • 1) there is a concentration gradient of an ion
  • 2) there is an open channel in the membrane so the ion can move from one side to the other

The Sodium Pump Sets Up Gradients of Na and K Across Cell Membranes

• All cells have the Na pump in their membranes
  • Pumps 3 Nas out and 2 Ks in for each cycle
  • Requires energy from ATP
    • Uses about 30% of body's metabolic energy
  • This is a form of active transport- can pump ions "uphill", from a low to a high concentration
  • This produces concentration gradients of Na & K across the membrane
  • Typical concentration gradients:

•  
• The ion gradients represent stored electrical energy (batteries) that can be tapped to do useful work
• The Na pump is of ancient origin, probably originally designed to protect cell from osmotic swelling

Inhibited by the arrow poisons ouabain and digitalis