Researchers have known for a century that cobra venom affects the heart. But a University of Idaho biochemistry professor may be the first to learn the nature of the relationship between ticker and toxin.
What William Trumble and his team have discovered so far is how the toxic component of cobra venom - a protein called cardiotoxin - causes calcium to be released into the heart muscle cell, causing the heart to contract.A number of diseases, including muscular dystrophy, malignant hypothermia and hypertension, can result from an improper regulation of calcium, Trumble said.
"If we can understand the process of how a normal cell works, it will be easier to be able to recognize and correct a malfunction," he said. "Cardiotoxin is our tool to study calcium regulation in normal hearts."
A mammal's heartbeat, and all muscle action, is controlled by calcium entering and leaving muscle cells. Heart muscle cells contract when calcium enters and relax with it leaves. Trumble said the heart uses calcium both from outside the muscle cell and from a reservoir, called the sarcoplasmic reticulum, within the muscle cell itself.
His research has discovered that cobra venom cardiotoxin causes the reservoir's calcium-release channel to open, and the release of calcium then contributes to the heart muscle contracting.
Composed of only 60 amino acids, the cardiotoxin of the cobra venom is a fairly small protein, Trumble said. And because it is a protein, it can be modified.
"We want to find out if a protein with a different structure also has a different function in its ability to control the heartbeat," he said. "If you can control the calcium, you can control the way the heart beats."
Trumble and his team know some part of the cardiotoxin sets up reactions that cause calcium to move from the sarcoplasmic reticulum into the cell itself. By modifying the cardiotoxin protein, they are trying to find the simplest active part of the protein that affects the process and why that particular structure is important.
Cardiotoxin binds to proteins already in place in the membrane of heart cells, and somehow the association of cardiotoxin with certain membranes causes the release of calcium, Trumble said.
"First, we'd like to use cardiotoxin to identify which of the proteins it binds to are important in causing the channel to open. This may help tell us where the pieces of the puzzle go," he said. "Then if we change the shape of the cardiotoxin molecule - by altering its amino acids - and that changes its ability to open the channel, we may learn more about the mechanism of calcium release."
Trumble has been working on cardiotoxin research for about 21/2 years.