Which event does not belong in the steps involved in excitation-contraction coupling in skeletal muscle: ATP (adenosine triphosphate) hydrolysis, binding of calcium to calmodulin, conformational change in the dihydropyridine receptor, or depolarization of the Transverse Tubule (T-tubule) membrane?

Excitation-Contraction Coupling in Skeletal Muscle: The Exception

The binding of calcium to calmodulin is NOT a required step in skeletal muscle excitation-contraction coupling. In skeletal muscle, calcium binds directly to troponin C on the thin filament to initiate contraction, not to calmodulin 1, 2.

Understanding the Correct Events in Skeletal Muscle EC Coupling

Events That DO Occur:

Depolarization of T-tubule membrane is the initiating event where action potentials propagate along the transverse tubular system 2, 3. This depolarization is essential for voltage sensing and represents the first step in the coupling process 4.

Conformational change in dihydropyridine receptor (DHPR) occurs as the voltage sensor responds to T-tubule depolarization 2, 3. The DHPR undergoes voltage-dependent transitions that directly communicate with ryanodine receptors (RyR1) through physical protein-protein interaction 5. This conformational change is the critical link between electrical excitation and calcium release 3.

ATP hydrolysis is absolutely required for muscle contraction as it powers the cross-bridge cycling between actin and myosin filaments 4. ATP is also necessary for calcium reuptake into the sarcoplasmic reticulum by SERCA pumps, allowing muscle relaxation 4.

The Key Distinction: Calmodulin vs. Troponin C

In skeletal muscle, calcium released from the sarcoplasmic reticulum binds to troponin C, not calmodulin 1, 6. This is a fundamental difference from smooth muscle, where calmodulin plays the primary role in calcium-mediated contraction 4.

• Calmodulin can modulate RyR1 and DHPR function as a regulatory protein, but this is not part of the direct excitation-contraction coupling pathway 1, 6
• Calmodulin acts as a partial agonist when calcium-free and an inhibitor when calcium-bound, but these are modulatory effects, not essential coupling steps 1
• The essential calcium-binding protein for skeletal muscle contraction is troponin C on the thin filament 4

The Complete Skeletal Muscle EC Coupling Sequence:

1. T-tubule depolarization triggers voltage sensing 2
2. DHPR conformational change transmits signal to RyR1 via direct physical coupling 3, 5
3. Calcium release from sarcoplasmic reticulum through RyR1 channels 2
4. Calcium binds to troponin C (NOT calmodulin), causing conformational changes that expose myosin-binding sites on actin 4
5. ATP hydrolysis powers cross-bridge cycling and muscle contraction 4

Answer: Option 2 - binding of calcium to calmodulin is the event that does NOT belong in skeletal muscle excitation-contraction coupling 1, 6.