A specific protein isolated from the venom of a Chilean tarantula by UB biophysicists shows promise as the basis for new drugs for preventing atrial fibrillation, the chaotic beating of the heart that is a major cause of death following a heart attack.

In a study published this month in Nature, Frederick Sachs, professor of physiology and biophysics, along with researchers from Georgetown University, report they were able to prevent atrial fibrillation in rabbit hearts by an infusion of a peptide isolated from tarantula venom.

This is the first time that the physiological function of mechanosensitive ion channels has been demonstrated in the heart.

The work is an example of how basic research can lead to clinical payoffs, Sachs stated. "No one in their right mind would have sought to block atrial fibrillation with spider spit," he said. "We did it backwards. Since we had found venom worked on single molecules, we predicted it would also work on cells, tissues and organs. And it did.

"This is a first step toward developing a new class of drugs that may be applied to cardiac pathology and to the pathology of other organs."

Sachs and postdoctoral researcher Tom Suchyna at UB's Center for Single Molecule Biophysics, along with colleagues at the University of Virginia, Michigan State and NPS Pharmaceuticals Inc., reported isolating the protein last May. At that time, they suggested that it might have many uses, based on its ability to block pores in cell membranes called stretch-activated channels. These channels, which derive their name from the fact that stretching the cell membrane causes them to open, are responsible for regulating the mechanical functioning of cells. Sachs and colleagues discovered these channels at UB in 1983 in skeletal muscle cells.

Stretch-activated channels have been implicated in functions as diverse as the senses of touch and hearing, blood pressure and volume regulation, and coordination of the voluntary musculature, as well as the contraction of heart muscle. Composed of 10 billion excitable muscle cells, the heart cells must contract in synchrony in order to pump blood effectively. When heart tissue becomes stretched through disease, trouble ensues.

The chambers of the heart expand, stretching cells. Furthermore, as a result of poor blood perfusion, cells swell, stimulating stretch-activated channels to open and allowing an influx of positive ions. This influx is an excitatory stimulus to the heart that disrupts the electrical balance, causing the cells to fire erratically. The tarantula-derived peptide, known as GsMtx-4, blocks this process.

The next phase of Sachs' research involves producing large amounts of the peptide by recombinant DNA technology and chemical synthesis, studying the mechanism of action, identifying other potential biological actions on stretch-activated channels and collaborating with a drug company in turning GsMtx-4 into a clinically useful drug.

The research was funded by grants from the National Institutes of Health, U.S. Army Research Office and NPS Pharmaceuticals Inc.