Excitation-Contraction Coupling

The three types of muscle cells (smooth muscle, cardiac muscle, skeletal muscle) utilize different mechanisms by which membrane depolarization results in muscle contraction, i.e., electromechanical coupling. In smooth muscle, Ca2+ ions entering through opening of voltage-gated Ca2+ channels or following release from the SR, bind to calmodulin.

The Ca2+-calmodulin complex activates myosin light chain kinase, and phosphorylation of myosin light chain initiates smooth muscle contraction. This is in contrast to cardiac and skeletal muscle, where contraction is triggered by a conformational change induced by Ca2+ handling. In cardiac muscle, opening of voltage-gated Ca2+ channels results in Ca2+. In skeletal muscle, depolarization of the T tubule triggers release of Ca2+ from the SR. 

In contrast to cardiac muscle, skeletal muscle contractions can summate during repeated stimulation, resulting in an increase in force with incomplete relaxation between the stimuli (tetanic contraction). This difference is due to the much shorter action potential duration in skeletal muscle compared to cardiac muscle.

In all striated muscle (including cardiac muscle), membrane depolarization results in release of calcium from the sarcoplasmic reticulum into the cytosol. This calcium can then bind to troponin associated with the actin-containing thin filaments, resulting in sliding of thick and thin filaments and sarcomere contraction. 

Microtubules play no role in excitation-contraction coupling. Action potentials are propagated by the sarcolemma as an essential step in excitation-contraction coupling. Ca++ release from the sarcoplasmic reticulum is necessary for excitation-contraction coupling. The motor end plate is the site of neuromuscular transmission, the first stage of excitation-contraction coupling. T-tubules provide an electrical link whereby action potentials trigger Ca++ release from the sarcoplasmic reticulum.

D i.e. Tropomyosin

B i.e. Calcium binding troponin C

• In the resting state of skeletal muscle tropomyosin molecule lie on top of active sites of actin filamentsQ, so that attraction cannot occur between actin & myosin filaments to cause contraction.

Mechanism of contraction: when Ca²⁺ are released during the contraction process, the troponin complex undergoes a confirmational change that in some way shifts the tropomyosin molecules into the groove between the two actin strands. This uncovers the active sites on actin thus allowing myosin to bind the actin & contraction proceed.

• In resting skeletal muscle tropomyosin (a long filamentous protein) covers the active sites of actin filament where myosin head binds to actin^g. So that the attraction cannot occur between actin and myosin filaments to cause contraction.
• Initiation of muscle contraction occurs, when Ca⁺⁺ binds toroponin CQ. Binding causes lateral displacement of tropomyosin into the groove between two actin filaments. This uncovers active sites on actin thus allowing myosin head to bind the actin and contraction proceeds.

B & C i.e. Dephosphorylation causes definite relaxation & LC phosphatase is essential for binding

D i.e. IP3- DAG

During smooth muscle contraction increase in cytosolic calcium is due to influx through voltage or ligand gated plasma membrane Ca++ channelsQ and release of Ca⁺⁺ from sarcoplasmic reticulum activated by 1P3 receptor calcium channelsQ

– Different source of calcium

– As in skeletal & cardiac muscle, Ca⁺⁺ plays a important role in initiation of contraction but the source of Ca^.* increase is much different

– Unlike skeletal & like cardiac muscle most of the calcium which enters sarcoplasm comes from ECF and very little comes from sarcoplasmic reticulumQ. So the source of ca— are:

• Phosphorylation of myosin is essential for its binding to actin

Lack of troponin in smooth muscles prevents Ca’* activation via troponin binding. Rather Ca** binds to calmodulin and resulting complex activates calmodulin dependent myosin light chain kinase (MLCK). This enzyme catalyzes the phosphorylation of myosine light chain on serine at position 19

Myosin LC₂₀ phosphorylation is a must and increases myosin ATPase activityQ resultingin binding of myosin to actin and contraction . However, phosphorylation & dephosphorylation of myosin also occur in skeletal muscle but phosphorylation is not necessary for activation of ATPase

• Dephosphorylation & Latch bridges

Myosin LC is dephosphorylated by myosin light chain phosphatase but it does not necessarily Vt relaxation & final detachmentQ of myosin cross bridges from actin until the intracellular concentration of   falls below a critical level.

This continued attachment of myosin cross bridges to actin even after dephosphorylation creates latch bridges

Latch bridges do not make significant cycles of attachment & detachmentQ between actin & myosin so do not require much ATPQ and so maintain prolonged contractions without expenditure of much energy.

• If epinephrine or NE is added, the membrane potential becomes larger, the spikes decrease in frequency & muscle relaxes. Whereas acetylcholine addition 1/t decreased membrane potential, spikes become more frequent, muscle becomes more active with an increase in tonic tension & number of rhythmic contractions.

During smooth muscle contraction increase in cytosolic calcium is due to influx through voltage or ligand gated plasma membrane Ca++ channelsQ and release of Ca⁺⁺ from sarcoplasmic reticulum activated by 1P3 receptor calcium channelsQ

A i.e. Troponin (+ve)

A i.e. Inositol triphosphate

Inositol triphosphate diffuses to the endoplasmic reticulum, where it triggers the release of calcium into cytoplasm.

Inositol triphosphate and diacylglycerol (DAG) both of which are second messengers, are associated with Gq subset of G protein mediated receptors.

Ans. d. Calcium binds to tropomyosin to initiate muscle contraction

Calcium binds to Troponin C, not to the tropomyosin, to initiate muscle contraction.

`The calcium released into the cytosol binds to Troponin C by the actin filaments, to allow cross-bridge cycling, producing force and, in some situations, motion.’