Muscle contraction physiology

So how does a muscle contract? In order to answer this question, we must first examine what tells a muscle to contract. Let’s say that I am sitting here writing and want to pick up a cup of coffee. In order to do so I must send a command to the muscles in my arm. The command comes from a thought generated in my nervous system. The command travels from my brain to my spinal cord to a nerve that attaches to a muscle in my arm. The command tells my muscle to contract and my arm dutifully responds by moving closer to the coffee.

Muscles are made of protein. If we were to examine a skeletal muscle under a microscope we would see that it is composed of tiny protein fibers or filaments. When a muscle receives a command from the nervous system to contract the protein filaments slide past each other. In fact one of the filaments connects to the other and drags it along. Think of thousands of overlapping filaments sliding past each other as the muscle contracts.

The command to contract must somehow get from the outside of the muscle to the inside. Tiny messengers called neurotransmitters bring the message from the nerve to the muscle. Other chemical messengers that tell the protein filaments to contract then pass on the message.

Muscles need energy to contract. Muscles must have some sort of power source in order to power the sliding filaments. The energy comes from ATP. ATP connects to one type of filament and extracts the energy so that it can pull the other filament along.

Let’s begin with an overview of the first part of the process of muscle contraction: the connection between the nervous system and a skeletal muscle.

A motor neuron connects to a skeletal muscle at a special area called the motor end plate.

The motor end plate has a folded structure and there is a gap or synaptic cleft between the axon terminal of the axon and the motor end plate on the muscle.

See the image below. An action potential (1) in the motor neuron will cause the influx of calcium into the axon terminal (2) which promotes the release of the neurotransmitter acetylcholine from the axon terminal (3). Acetylcholine moves across the synaptic cleft to the motor end plate (4) and promotes the opening of sodium channels causing sodium to rush into the skeletal muscle cell (5).

At rest, skeletal muscle is polarized and the movement of sodium causes it to depolarize.

This has an effect on the sarcoplasmic reticulum (6).

The sarcolemma surrounding the muscle cell contains tube like structures called T-tubules. The T-tubules reach into the muscle fiber and encircle the sarcomere. Since the T-tubule connects to the outside of the cell it is filled with extracellular fluid. Between T-tubules lies a specialized type of endoplasmic reticulum called the sarcoplasmic reticulum. The sarcoplasmic reticulum is a network of membranous channels called cisternae. Cisternae near the T-tubules are wider and called terminal cisternae. A tubule and the two adjacent terminal cisternae are called a triad.

The sarcoplasmic reticulum actively transports calcium so it contains a high concentration of calcium. The concentration of calcium inside the sarcoplasmic reticulum is 2000 times greater than inside the muscle cell. So a significant calcium gradient exists between the sarcoplasmic reticulum and the inside of the muscle cell.

The sarcoplasmic reticulum responds to the depolarization of the muscle cell by opening calcium channels in the terminal cisternae of the sarcoplasmic reticulum. When these channels open calcium rushes into the sarcoplasm of the muscle cell. This process is called excitation-contraction coupling.

To summarize, the sarcoplasmic reticulum is a network of tubules that wraps around the muscle cell. Think of a loosely knit winter sweater.

The sarcoplasmic reticulum will take calcium from the blood and store it until the muscle cell depolarizes. Once it does, the sarcoplasmic reticulum releases calcium into the muscle cell.

So, before we go any further, we need to take a look at the structure of the protein filaments inside of the muscle cell.

There are 2 important contractile proteins in muscle cells. One is called actin or the thin filament and the other is called myosin or the thick filament. Actin is a double helix protein and myosin has large globular protein heads.

The actin and myosin are arranged in an overlapping arrangement with actin on the outside of myosin.

There is another double helix protein complex wrapped around actin called the troponin-tropomyosin complex.

In the middle of this structure there is only myosin which is called the m line and at the ends there are the z lines. The entire contractile unit between the Z lines is called a sarcomere.

The goal is to get actin and myosin to connect and slide past each other so the sarcomere contracts.

Once calcium is released by the sarcoplasmic reticulum, calcium rushes into the sarcoplasm of the muscle cell and attaches to the troponin on the troponin-tropomyosin complex wrapped around the actin. This causes a change in the position of the troponin that exposes the myosin binding site on the actin. The myosin can now bind with actin forming what is known as a cross-bridge.

Myosin can now move at its hinge region and subsequently move the actin along. This results in actin and myosin sliding past each other. At the end of a cycle of movement the myosin must release from actin and return to its original position. It can now repeat the cycle and bind with another site on the actin. The cycle consists of cross-bridge formation, movement, release and myosin’s return to its original position. This cycle is called cross-bridge cycling.

The energy needed for one cross-bridge cycle is provided by one ATP molecule. ATP binds to the myosin head which has ATPase activity. The ATP decomposes into ADP and a phosphate. Once the calcium attaches to troponin and exposes the binding site the myosin moves and binds to actin while releasing the phosphate and extracting the energy from the phosphate bond. ADP is released from the myosin head when myosin pulls actin along. Another ATP must again bind to the myosin head to allow for release of the myosin head from actin. ATP binds to the myosin head and decomposes into ADP and phosphate which remain on the myosin head. The myosin head now releases from actin and resumes its resting position with the ADP and phosphate still on it. The energy from the ATP is stored in the myosin head.

Movement of the myosin head while it is attached to actin is called the power stroke while movement of the myosin head back to its original position is called the recovery stroke.

Resting muscles store energy from ATP in the myosin heads while they wait for another contraction.