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New Pathway Critical to Heart Arrhythmia

New Pathway Critical to Heart Arrhythmia

Photo: Medical book and stethoscope

The study examined the electrical impulses that coordinate contraction in heart and skeletal muscles, controlling heart rate, for example. Unravelling how the body regulates these impulses is key to understanding serious health conditions such as paralysis, muscle relaxation and heart arrhythmia.

Researchers in the Cell study examined ion channels — membrane proteins that allow the electrical charges to flow into and out of the cell. The number and location of channels on the cell's surface are critical to the heart's rhythm. The scientists found a new, previously unknown intracellular trafficking pathway that controls the number and location of the ion channels on the cell surface, affecting the passage of electrical charges and controlling the beat of the heart and other muscle activity.

Ion channels are proteins that form pores at the cell's surface. The pores open with careful regulation, allowing the passage of ions like potassium, sodium or chloride. These ions carry distinct electrical charges, and their regulated passage into and out of the cell stimulate and coordinate contractions such as the heart's rhythm.

"This study illuminates a new pathway for therapeutic intervention," says Doctor Paul Welling. "Drugs that interfere with or augment this signal may be used to control the number and location of ion channels in such a way to fight arrhythmia and other muscle disorders, potentially saving lives."

Welling and his colleagues examined the molecular pathology of the genetic condition Andersen-Tawil Syndrome, characterised by uncoordinated muscle contractions, paralysis and disruptions in the normal heart rhythm. The syndrome is caused by mutations in the gene known as KCNJ2, which encodes a potassium channel in the heart and skeletal muscle known as Kir2.1.

The scientists examined how mutations in the potassium channel affects its passage through a key intracellular sorting station called the Golgi apparatus. The Golgi apparatus modifies, sorts and packages molecules for the cell's use. Welling's lab found that the Golgi apparatus selects the Kir2.1 channel to travel to the surface of the cell in an unusual, signal-dependent manner. The signal determines where the Golgi apparatus sends the potassium channel and how many it sends and verifies that the channels are of quality. In patients with Andersen-Tawil Syndrome, the signal is faulty and fails to properly regulate the ion channels and their path to the cell surface.

MEDICA.de; Source: University of Maryland School of Medicine

 
 
 

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