Although the sight of a large hairy spider is enough to give some people a heart attack, spider venom may eventually be used to treat some heart conditions. In the 4 January issue of Nature, Bode et al. (Nature, 409, 35–36) report that a peptide isolated from the venom of the spider Grammostola spatulata (picture) inhibits atrial fibrillation. Atrial fibrillation, characterized by disorganized atrial activity, occurs in patients suffering from valve disease, hypertension, and chronic lung disease. It is the most common form of cardiac arrhythmia, and can lead to further complications such as hypotension, pulmonary congestion, strokes and angina pectoris.
The anti-arrhythmic effects of this peptide were discovered serendipitously in a research project that initially had nothing to do with hearts or spiders. Frederick Sachs, senior author on the study, began investigating mechanosensitive ion channels over 15 years ago. In a search for agents that block or activate mechanical sensitivity, his group began screening insect venoms, which are known to contain a variety of neuroactive compounds. “We tried a variety of spider and scorpion venoms in patch clamp experiments, and finally found two that inhibited mechanosensitive ion channel activity,” said Sachs. Fractionation of the venom led to the isolation of a peptide from tarantula venom, GxMtx-4, that the authors observed to block the activity of cationic stretch-activated ion channels (SACs) in adult astrocytes and cardiocytes.
SACs convert gradients of stress into gradients of electrical activity, and sustained mechanical gradients can develop when systolic pressure and wall tension are high, conditions that are present in the diseased heart. “It was well-known that cardiac wall stretch increases heart rate, and we knew that these receptors were expressed in heart cells,” said Sachs. He teamed up with Frank Bode and Mike Franz at Georgetown University to show that the peptide suppressed both the incidence and duration of atrial fibrillation in rabbit hearts. They also showed that GxMtx-4 acts only during stretch activation, as it has no effect on the action potential of resting atrial cells. “It also seems to have no acute effects on normal hearts in the absence of distension,” added Sachs, although further toxicity analysis is required.
This finding of Bode et al. constitutes the first demonstration that SAC activation can generate atrial fibrillation. The authors therefore suggest that GsMtx-4 initiates a new class of anti-arrhythmic agents that could act on the cause, rather than the effects of cardiac arrhythmias.
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Novak, K. Spider venom helps hearts keep their rhythm. Nat Med 7, 155 (2001). https://doi.org/10.1038/84588
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