Action Potentials and Muscle Contraction

A muscle contraction (also known as a muscle twitch or simply twitch) occurs when a muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten or remain the same. Though the term 'contraction' implies a shortening or reduction, when used as a scientific term referring to the muscular system contraction refers to the generation of tension by muscle fibers with the help of motor neurons. Locomotion in most higher animals is possible only through the repeated contraction of many muscles at the correct times. Contraction is controlled by the central nervous system (CNS), which comprises the brain and spinal cord. Voluntary muscle contractions are initiated in the brain, while the spinal cord initiates involuntary reflexes.

• An action potential originating in the CNS reaches an alpha motor neuron, which then transmits an action potential down its own axon.
• The action potential activates voltage-dependent calcium channels on the axon, and calcium rushes in.
• Calcium causes vesicles containing the neurotransmitter acetylcholine to fuse with the plasma membrane, releasing acetylcholine into the synaptic cleft between the motor neuron terminal and the motor end plate of the skeletal muscle fiber.
• The acetylcholine diffuses across the synapse and binds to and activates nicotinic acetylcholine receptor on the motor end plate. Activation of the nicotinic receptor opens its intrinsic sodium/potassium channel, causing sodium to rush in and potassium to trickle out. Because the channel is more permeable to sodium, the muscle fiber membrane becomes more positively charged, triggering an action potential.
• The action potential spreads through the muscle fiber's network of T-tubules, depolarizing the inner portion of the muscle fiber.
• The depolarization activates L-type voltage-dependent calcium channels (dihydropyridine receptors) in the T tubule membrane, which are in close proximity to calcium-release channels (ryanodine receptors) in the adjacent sarcoplasmic reticulum.
• Activated voltage-gated calcium channels physically interact with calcium-release channels to activate them, causing the sarcoplasmic reticulum to release calcium.
• The calcium binds to the troponin C present on the actin-containing thin filaments of the myofibrils. The troponin then allosterically modulates the tropomyosin. Normally the tropomyosin sterically obstructs binding sites for myosin on the thin filament; once calcium binds to the troponin C and causes an allosteric change in the troponin protein, troponin T allows tropomyosin to move, unblocking the binding sites.
• Myosin (which has ADP and inorganic phosphate bound to its nucleotide binding pocket and is in a ready state) binds to the newly uncovered binding sites on the thin filament (binding to the thin filament is very tightly coupled to the release of inorganic phosphate). Myosin is now bound to actin in the strong binding state. The release of ADP and inorganic phosphate are tightly coupled to the power stroke (actin acts as a cofactor in the release of inorganic phosphate, expediting the release). This will pull the Z-bands towards each other, thus shortening the sarcomere and the I-band.
• ATP binds myosin, allowing it to release actin and be in the weak binding state (a lack of ATP makes this step impossible, resulting in the rigor state characteristic of rigor mortis). The myosin then hydrolyzes the ATP and uses the energy to move into the "cocked back" conformation. In general, evidence (predicted and in vivo) indicates that each skeletal muscle myosin head moves 10-12 nm each power stroke, however there is also evidence (in vitro) of variations (smaller and larger) that appear specific to the myosin isoform.
• Steps 9 and 10 repeat as long as ATP is available and calcium is present on thin filament.
• While the above steps are occurring, calcium is actively pumped back into the sarcoplasmic reticulum. When calcium is no longer present on the thin filament, the tropomyosin changes conformation back to its previous state so as to block the binding sites again. The myosin ceases binding to the thin filament, and the contractions cease.
• The calcium ions leave the troponin molecule in order to maintain the calcium ion concentration in the sarcoplasm. The active pumping of calcium ions into the sarcoplasmic reticulum creates a deficiency in the fluid around the myofibrils. This causes the removal of calcium ions from the troponin. Thus the tropomyosin-troponin complex again covers the binding sites on the actin filaments and contraction ceases.

Nerve Impulse

The conduction of nerve impulses relies upon the movement of electrically charge ions across the nerve cell membrane. When a nerve is resting, or polorized, there are more potassium ions than sodium ions inside the cell, with an opposite ratio outside. Sodium ions are actively kept out of the cell by an energy consuming pump mechanism. This maintains a negative charge on the inside of the cell and a positive charge on the outside. When an impulse travels along the nerve, sodium ions flood into the cell and make the inside of the cell positive with respect to the outside. This produces a rise in the electrical potential across the cell membrane. After the impulse has passed, potassium ions leave the cell, restoring the negative charge within the cell and the positive charge outside it. While this resting situation is being restored another impulse cannot be generated.

Ion Conductances

The generation of action potentials is mainly due to the changes of sodium (Na+) and potassium (K+) conductances. Figure 2 shows the concentrations of Na+ and K+ ions on both sides of a nerve membrane. For Na+, its concentration on the extracellular side is much higher than inside. We immediately notice that Na+ ions are far from electrochemical equilibrium -- both the electric force due to electric potential difference and the chemical force due to ion concentration difference are pointing inward. How could the nerve membrane maintain such a stable state? This is because the conductance of Na+ ions in the membrane is very small at the resting membrane potential. Although the inward driving force is large, the resulting Na+ influx is small. This small influx can be balanced by a slow ion transport process, the Na+-K+ pump, which moves the Na+ ions outward and simultaneously the K+ ions inward.

The conductance of Na+ ions may change dramatically with the membrane potential as demonstrated by voltage clamp experiments, in which the membrane potential is displaced to a new value and maintained there . Because ions carry charges, the movement of ions across the membrane will change the membrane potential. To maintain a constant membrane potential, the voltage clamp circuit must generate electric currents to neutralize the membrane potential change caused by the ionic flux. Thus, the ion current through the membrane is reflected in the electric current of the voltage clamp circuit outside the membrane

Action potential and Epilepsy