Tarantula peptide inhibits atrial fibrillation

Solution Structure of Peptide Toxins That Block Mechanosensitive Ion Channels

“…A natural abundance 1 H, 15 N HSQC experiment provided a fingerprint of the amide nitrogen and amide proton correlation for each residue except proline (Fig. 2).…”

“…It may act to stabilize the patch and/or facilitate folding and disulfide formation. Adding to speculation that the hydrophobic patch may be involved in binding, Phe 5 in GsMTx-4 was the only amino acid besides the terminal glycines and prolines that could not be assigned in the 1 H, 15 N HSQC spectrum of GsMTx-4 ( Fig. 2).…”

“…A DIPSI-2 (27) sequence of 60 -90 ms was used in the TOCSY experiments, and a 150-ms mixing period was used in the NOESY experiments. Two-dimensional 1 H, 15 N HSQC and 1 H, 13 C HSQC (28) spectra were acquired with natural abundance proteins. Data were processed either with a modification of version 2.3 of Felix software (Accelrys, Inc.) or NMRPipe (29).…”

“…The more potent of these toxins, GsMTx-4, not only blocks MSC currents seen with patch clamp recording but exhibits effects at the cellular level that appear to involve MSC activation. GsMTx-4 can reduce the cell size in swollen and hypertrophic heart cells, decrease volume-activated currents in astrocytes (14), and inhibit stretch-induced arrhythmias in the heart (15).…”

Mechanical Effects on Cardiac Activity

“…These results suggest that chronic activation of I Cir,swell may underlie the genesis of SD in failing ventricular myocytes and may potentiate triggered cardiac arrhythmias in the setting of heart failure. Novel blockers of I Cir,swell such as GsMTx-4, which inhibits atrial fibrillation in an isolated, perfused rabbit heart model (Bode et al 2001), also may be efficacious in preventing the triggered arrhythmias seen in CHF.…”