Excitation-Contraction Coupling (ECC)
- Definition: Coupling electrical stimulation of muscle membrane with muscle contraction.
Key Structures | ㅤ |
Sarcolemma | Muscle membrane |
T-tubules | Invaginations of sarcolemma |
Sarcoplasmic reticulum (SR) | Calcium storage |
ㅤ | Skeletal Muscle ECC | Cardiac Muscle ECC |
Coupling type | Mechanical coupling or Electromechanical coupling | Chemical coupling or Electrochemical coupling |
Calcium Source | 100% source is SR | Calcium-induced calcium release ICF calcium (80%) ECF calcium (20%) |
DHPR (Dihydropyridine receptor) ↳ (T-tubule membrane) | CaV1.1 ↳ ⛔ by Dihydropyridine CCBs ↳ Amlodipine, Nifedipine | CaV1.2 |
RyR (Ryanodine receptor) ↳ (SR membrane) | RyR1 ↳ Beneficial Positive Feedback | RyR2 |
ㅤ | ㅤ | Lysosomes are absent in heart muscles |
Mnemonic | Skeletal Muscle → Mechanical activity → Electromechanical coupling | Cardiac → electrical activity → Electrochemical coupling |
- Skeletal Muscle ECC Mechanism:
- Depolarization travels down T-tubules → Activates DHPR channels → DHPR structurally changes → Physically (mechanically) interacts with and twists RyR1 channels → RyR1 channel opens (forms pore) → Calcium from SR flows into cytoplasm → Increased cytoplasmic calcium → Skeletal muscle contraction.
- Cardiac Muscle ECC Mechanism:
- Depolarization of cardiac membrane → Activates DHPR (CaV1.2) → DHPR opens up first → ECF calcium enters cytoplasm (small, essential amount) → ECF calcium stimulates RyR2 on SR (chemical stimulation) → Stimulated RyR2 channels open → Larger amount of calcium released from SR into cytoplasm.
Diseases Related to RyR1 Mutation (Skeletal Muscle)
Mutation of RyR1 | Gain of function | Loss of function |
Disease | Malignant Hyperthermia | Central Core Disease |
Effect | Excessive calcium release ↳ Severe muscle contraction ↳ Heat production | Less calcium release ↳ hypotonia ↳ weakness |
Treatment | Dantrolene ↳ RyR1 antagonist | No specific treatment |
Precipitated by | Anesthetic agents (e.g., halothane) | ㅤ |
Mnemonic | Ryan has gained fever and cancer (malignant hyperthermia) and dandruff (Dantrolene) | Ryan already lost (Loss of function) his Core strength (Central core disease) when born → hypotonia, weakness |
Mechanism of Muscle Contraction
ㅤ | Steps in Muscle Contraction | Notes |
Trigger | ↑↑ free calcium in cytoplasm | ㅤ |
Calcium Binding | Type of muscle | Calcium binds to |
ㅤ | Skeletal & Cardiac Muscle | Troponin C |
ㅤ | Smooth Muscle | Calmodulin Mnemonic: Smooth Kaalu |
After Ca2+ binding | Following Steps | Description |
ㅤ | Cross-bridge formation | Myosin heads attach to actin |
ㅤ | Power stroke | Myosin head pulls actin filament towards center (From 90° to 45° angle) ⇒ muscle contraction |
ㅤ | Detachment | Requires ATP |
- NOTE: Calbindin:
- Calcium-binding protein
- Regulates calcium homeostasis
- Not involved in Muscle contraction
Sarcomere Structure and Proteins
Zones | Notes |
Center | • M line (center of myosin filaments). |
Sarcomere | • 1 sarcomere = length between 2 Z lines |
H zone | • between two actin fliaments • decrease during contraction |
A zone/band | • Length of myosin filament • remains constant |
- Mnemonic:
- “ZIA → HM”🗸🗸
- H → Disappear
- A → Constant
- I → Short (I short)
- MMAZAI
- MMA → M line → Myosin → A band
- ZAI → Z line → Actin → I band
Key Proteins: | Location | Function | Mutations |
Titin | From M line to Z line Tightly between M and Z line | Muscle elasticity | DCM, HCM, Tibial anterior myopathy (skeletal) |
Alpha-actinin | Holds actin to Z line Actin → alpha gen/ Z gen | ㅤ | ㅤ |
Nebulin | Fence-like barrier around actin till tip of Z line Nebula → revolves around active sun (actin) | Maintains actin length | Nemaline Myopathy |
LENGTH TENSION RELATIONSHIP GRAPH :
Muscle Contraction Frequency and Tetanus
ㅤ | Stimulation | Effect |
Single twitch | Single stimulation | Single contraction and relaxation |
Summation / Incomplete tetanus | Repeated stimulations with partial relaxation between contractions Women can be summed up as incomplete | Increased contraction height |
Complete tetanus (or titanization) | Very high-frequency repeated stimulations with no relaxation Men are titans | Sustained, persistent contraction |
Tetanizing frequency:
- Frequency to produce complete tetanus.
- Calculation:
- 1
Contraction period (in seconds) - 1000
Contraction period (in ms)
- Example:
- Contraction period = 40 ms → Tetanizing frequency = 1000/40 = 25 Hz.
Q. The given image displays a basic muscle twitch and its corresponding time trace, which was recorded in a frog exhibiting the lowest frequency required for tetanization. (The time trace was obtained using a tuning fork with a frequency of 100 Hz.)
A. 25 per second
B. 15 per second
C. 17 per second
D. 20 per second
B. 15 per second
C. 17 per second
D. 20 per second
- Find time from B to C
- Freq = 100Hz ⇔ 1 vibration = 0.01 sec
- B to C → has 5 vibrations → 5 x 0.01 = 0.05
- So, TF = 1/0.05 = 20Hz
Muscle Fibres
- 1 slow Red Ox
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