Nerve & Muscle Physiology

·         The A band contains the thin filaments (actin) and the thick filaments (myosin).

The H band is the portion of the A band that contains only myosin, and the I band is the portion that contains only actin.

The actin is anchored at the Z line.

·         Serotonin: Brain Stem

Histamine: Hypothalamus

·         In neuronal endplate, AP coming at Pre Synaptic plate->Release of Ach from Pre Synaptic terminal is due to Ca⁺⁺, AP at Post Synaptic terminal is due to influx of both Na & K (esp. NICOTINIC RECEPTOR). Unlike other place where just Na.

·         Glycine (PNS), GABA (CNS): inhibitory by increasing Cl- conductance

·         NO: inhibitory

·         Glutamate, Aspartate : Excitatory

They act through: AMPA- Na & K conductance

NMDA-Na,Ca,K conductance also aomewhat voltage dependant

·         Actions of Sarcomere during contraction

Sarcomeres get smaller

H & I bands get smaller (HI)

Distance b/w Z lines gets smaller

A band no change

Force and Tension ↑ as length ↓

·         2 ATPases are involved in one  stimulus, not 2 ATP.

·         Passive tension PT(Preload) is proportional to length.

Active tension AT (Afterload) inversely proportional to length, proportional to number of cross-bridges.

Lo(Optimum Length) is point in PT curve that corresponds maximum AT. Optimum Tension is tension required to produce that PT.

TT= PT+AT

·         SKM lacks volatage gated Ca++ Channel, which are present in Cardiac & Smooth muscle.

·         We can tetanize SKM bcoz 1. Narrow APD and 2. Time lag

·         Nerve and skeletal muscle membranes contain Na+ and K+ ion selective channels.

Cardiac muscle membranes contain Na+, K+, and Ca2+ ion selective channels.

·         Na⁺ is necessary to depolarize every membrane in the body except the Atrium that uses Ca²⁺.

·         Conductance of K⁺ occurs more than any other ion at rest. à only K moves at rest freely. So it maintain resting potential.

·         Muscle Contraction requires no energy but the Calcium, Whereas muscle relaxation requires ATP.

At the end of Contraction, Ca²⁺ -ATPase pumps Ca²⁺ into the SR .Protein called phospholambin inhibits Ca-ATPase when its done.

• Without Phospholambin, Ca²⁺-ATPase activity will increase and pump intracellular Ca²⁺ back into SR.
• Cytoplasmic Ca²⁺ will decrease → Muscle weakness.
• There won’t be enough Ca²⁺ to cause contraction → Will die of respiratory failure.

·         Smooth muscle:

Has No troponin

• Actin and Myosin are always bound è Latching
• After you eat  → release Muscles and burn more ATP in the GI
• Sounds created by latching called Boborygmi (gut sounds)

Has no ATPase activity

• uses MLCK = myosin light chain kinase
• And MLCP = myosin light chain phosphatase

·         T-tubules of:

o   Cardiac muscle – is found in the z –line

o   Skeletal muscle – is found in AI junction

·         When dephosphorylated, the cross-bridges stay attached (or cycle slowly). The attached, slowly cycling cross-bridges are called latch bridges. Latch bridges allow smooth muscle to maintain force while minimizing energy expenditure.

·         Our muscles have 2 types of fibers:

1- Type I: slowly contracting, red, fatigue-resistant, rich in oxidative enzymes (and myoglobin, mitochondria, lipids, and local capillary density) but has low phosphorylase and glycogen contents. It has an oxidative metabolism. The erector spinae is an example.

2- Type IIa: Very rare human.

3- Type IIb: fast-twitching and fatigable, white, rich in phosphorylase and glycogen and it has a glycolytic metabolism.

·         Membrane excitability is related to the ease with which Na+ channels open when the cell is depolarized. The activation of Na+ channels or the opening of the m gate is governed in part by the extracellular Ca2+ concentration. When extracellular Ca2+1 is lowered, the m gate can open at more negative membrane potentials, and therefore the membrane is more easily excited. Although increasing extracellular K+ will bring the membrane closer to threshold and thus may make it more excitable, its predominant effect is to cause the inactivation of Na+ channels by the closing of the h gates. Inactivation of sodium channels makes the cell membrane less excitable. 

·         Phospholamban is a protein contained within the sarcoplasmic reticulum that inhibits the activity of the SR calcium pump. Inactivation of phospholamban results in an increase in calcium sequestration by the SR. In cardiac muscle, the rapid sequestration of calcium shortens the duration of the contraction. In smooth muscle, calcium sequestration causes the muscle to relax.

·         The amount of charge that must flow to produce this depolarization decreases as the capacitance decreases. Therefore, as the capacitance decreases, conduction velocity increases.

·         The amount of potassium leaking out of the cell depends on its driving force and its membrane conductance. The driving force is the difference between the membrane potential and the equilibrium potential for potassium. Since the membrane potential is more positive than the equilibrium potential for potassium, hyperpolarizing the membrane (that is, making it more negative) would reduce the driving force.

·         Phase-4 depolarization is caused by the activation of a Na+ channel. The channel is called the funny channel because it is activated when the membrane hyperpolarizes in contrast to the Na channel responsible for the action potential, which is activated when the cell depolarizes.

·         The firing of the alpha motoneurons to the biceps muscle produces rapid flexion of the arm. Because the arm is rapidly flexed, the Ia afferent neurons innervating the muscle spindles in the biceps, which detect muscle length, will reduce their firing rate. The Ib afferents, innervating the Golgi tendon organs (GTO) from the biceps, will detect the contractile activity of the biceps and increase their firing rate. The triceps are stretched during the arm flexion and so their Ia afferents will increase their firing rate. Ib afferents do not respond when muscles are passively stretched, so their firing rate will not change.

·         Muscle power or work-rate is the product of muscle force (afterload in N) and shortening velocity (m s-1). The maximal work rate of human muscles is reached at a contraction velocity of 2.5 m s-1. The maximal work-rate is thus (300 kPa *2.5 m s-1) = 750 kW per square meter of cross sectional area.

·         The stretch reflex includes (1) a monosynaptic excitatory pathway from group Ia (and II) muscle spindle afferent fibers to a-motor neurons that supply the same and synergistic muscles, and (2) a disynaptic inhibitory pathway to antagonistic motor neurons.

·         Typically, slow twitch muscles are recruited before fast twitch muscle fibers due to the greater excitability of motor neurons innervating slow twitch muscles. The high oxidative capacity of slow twitch muscle fiber supports sustained contractile activity. Fat twitch muscle fibers, on the other hand, tend to be large, and typically have low oxidative capacity and high glycolytic capacity. The fast twitch motor units are thus best suited for short periods of activity when high levels of force are required.

·         Adrenaline causes vasodilatation in the skeletal muscles but noradrenaline has no such effect. While adrenaline decreases the peripheral resistance of the blood vessels, noradrenaline increases it. However, both cause bronchodilatation.