Mg –Muscle Relaxant

Muscles 101

Mg in muscle contractions

Muscles 101

The function of muscles is to produce forceand cause motion - either as locomotion of the organism itself or movement of internal organs.

There are three classifications:

–   Skeletal muscle – anchored by tendons to bone to effect skeletal movement, such as locomotion or posture

–   Cardiac muscle – found only in the heart; responsible for pumping blood; similar to skeletal muscle

–   Smooth muscle – found within walls of organs/structures such as esophagus, stomach, intestines, bronchi, uterus, urethra, bladder, blood vessels; responsible for sustained contractions.

When referring to the muscular system, “contraction”means that muscle fibers generate tension with the help of motor neurons - We use our muscles by selectively contracting them:

–   Voluntary (conscious) contraction of skeletal muscle (controlled by action potential signals from the central nervous system)

E.g. movement of quadriceps muscle to kick a ball, or eye movement.

Occurs as a result of conscious effort originating in the brain, which sends action potential signals through the nervous system to the motor neuron that innervatesseveral muscle fibers. In the case of some reflexes, the signal to contract can originate in the spinal cord through a feedback loop with the brain's grey matter.

–   Involuntary (without conscious thought) contraction of cardiac or smooth muscle (non-conscious brain activity or stimuli from the body to the muscle) –necessary for survival.

E.g. contraction of the heart muscle for heartbeat, peristalsis (pushes food through GI tract)

Mg in muscle contractions

Calcium pumps move calcium

Plasma membrane Ca2+-ATPase (PMCA) pump – move calcium into and out of all eukaryote (nucleus-containing) cells; Ca2+ is an important second messenger (relays messages from membrane receptors to intracellular targets), so intracellular levels must be maintained at low concentrations to prevent noise, in order to have messages delivered properly (called cell signaling).

–    PMCA and the sodium calcium exchanger (NCX) arethe main regulators of intracellular Ca2+ concentrations -Since it transports Ca2+ into the extracellular space, the PMCA is also an important regulator of the calcium concentration in the extracellular space.

–    The PMCA pumps are powered by the hydrolysis of Mg-dependent ATP (One Ca2+ ion removed for each molecule of ATP hydrolysed) - PMCA binds tightly to (has high affinity for) Ca2+ ions but does not remove Ca2+ at a very fast rate, and is well-suited for maintaining Ca2+ at its normally very low levels. In contrast, NCX has a low affinity, but a high capacity and is thus better suited for removing large amounts of Ca2+ quickly, as is needed in neurons after an action potential.

Sarcoplasmic reticulum Ca2+-ATPase (SERCA) pump – in muscle cells, pump calcium,previously released from cell cytoplasm, back into the sarcoplasmic reticulum, a cell organelle that acts as a storage depot for calcium inside the muscle cell.

–   The SERCA pumps are powered by the hydrolysis of Mg-dependent ATP

MG IN Contraction/Relaxation of muscle

The electrical action potential signal in a muscle cell to initiate a contraction - involves complex movement of sodium and calcium ions into and potassium ions out of the muscle cell to propogate an action potential and depolarize the cell. There must then be a rapid restoral of the ions against their electrochemical gradients for the cell to repolarize and be ready for the next action potential.

The Mg-dependent Na/K pumps maintain appropriate intracellular/extracellular potassium/sodium ion concentrations

Mg –Cell “Battery”/ATP Production

Muscle Contraction (The Calcium Cycle) - occurs in response to a nerve's electrical action potential stimulus. Contraction of cardiac and smooth muscle requires rapid shifting of intracellular calcium ions to maintain appropriate gradients; a muscle contraction is initiated when intracellular calcium is released from the sarcoplasmic reticulumor calcium enters the cell from the outside.

Mg++ levels inside and outside the cell have an important role

in the intracellular calcium cycle in muscle cells

Muscle Relaxation - to relax a muscle, intracellular calcium is quickly pumped back into the sarcoplasmic reticulum via SERCA pumps and is pumped out of the cell via PMCA pumps after the calcium cycle is completed.

Mg-dependent Na/K-ATPase pumps are vital for production of mitochondrial ATP energy needed to enable SERCA pumps to quickly shunt Ca++ back into the sarcoplasmic reticulum and PMCA pumps to pump Ca++ out of the cell

Mg is a “Calcium Channel Blocker (for some cell membrane-bound calcium channels) - Mg++ serves as an important gating mechanism limiting the influx of extracellular calcium into the cytosol via PMCA pumps. (Mg is thus similar to calcium channel blocker drugs, which lower blood pressure by blocking calcium entry into heart and smooth muscle cells of blood vessels).

Mg limits the influx of extracellular calcium into the cell cytoplasm

Mg effects on cardiac system

Mg in skeletal muscle contractions