Question

Explain how the neuromuscular junction functions.

Describe the sliding filament model of muscle contraction.

Answer 1

Mechanism of Neuromuscular transmission:

Neuromuscular transmission is the transmission of an impulse from the motor neuron to the skeletal muscle fibres supplied by the neuron.

• Presynaptic events:

Presynaptic terminals resemble small round or oval knobs called terminal knobs or synaptic knobs. The terminal has neurotransmitter containing vesicles.

The membrane of the presynaptic terminal is called the presynaptic membrane. It contains large numbers of voltage-gated calcium channels.

The events that occur after the arrival of the action potential in the presynaptic terminal:

Action potential arrives at the axon terminal. Voltage-gated calcium channels open. Calcium enters the cell. Calcium signals to the vesicle.Vesicle moves to the membrane.Docked vesicles release neurotransmitters by exocytosis. The neurotransmitter diffuses across the synaptic cleft and binds to the receptors.

• Postsynaptic events:

At the postsynaptic membrane, neurotransmitter molecules bind to membrane-bound receptor molecules with recognition sites specific for that neurotransmitter.

Binding of the neurotransmitter to the receptor triggers a postsynaptic response specific for that receptor.

These responses can be either excitatory or inhibitory, depending on the properties of the receptor.

If receptor stimulation occurs in the postsynaptic membrane, it becomes more electrically positive (depolarized). It is an excitatory postsynaptic potential (EPSP). If the membrane becomes more negative (hyperpolarized), it is an inhibitory postsynaptic potential (lPSP).

Sliding filament model of muscle contraction:

Step 1: ATP binding

ATP binding to the myosin heavy chain (MHC) reduces the affinity of myosin for actin, causing the myosin head to release from the actin filament.

Step 2: ATP hydrolysis (resting stage of muscle)

The breakdown of ATP to ADP and inorganic
phosphate (Pi) occurs on the myosin head. As a
result of hydrolysis, the myosin head pivots around the hinge into a "cocked" position

Step 3: Cross-bridge formation

The cocked myosin head now binds to its new position on the actin filament.

Step 4: Release of Pi from the myosin

Dissociation of Pi from the myosin head triggers the power stroke, a conformational change in which the myosin head bends around 45 degrees about the hinge and pulls the actin filament around 11 nm toward the tail of the myosin molecule, thereby generating force and motion.

Step 5: ADP release

Dissociation of ADP from myosin completes the cycle, and the actomyosin complex is left in a rigid state (at a 45-degree angle). The ADP-free myosin complex remains bound to actin until another ATP molecule binds and initiates another cycle.

The cycle continues until the SERCA (SarcoplasmicEndoplasmic Ca-ATPase) pumps Ca2+ back into the SR. As Ca2+level falls, Ca2+ dissociates from troponin C, and the troponin-tropomyosin complex moves and blocks the myosin bind myosin-binding actin filament.

If the supply of ATP is exhausted, as occurs with death, the cycle stops in the state of permanent actin-myosin complexes (i.e., the rigor state). In this state the muscle is rigid and the condition is termed as rigor mortis.