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ProTx-I peptide was first isolated and characterized from the venom of tarantula Thrixopelma pruriens and consists of 35 amino acids.1 This peptide toxin belongs to the inhibitory cystine knot (ICK) family, which is known to interact with voltage-gated ion channels. ProTx-I does not effect the rate of inactivation of channels but modifies the conformation of channels to an open position by shifting voltage dependence to more positive potentials. In addition, this toxin, like other members of the ICK family of spider toxins, can bind multiple voltage-gated ion channel families. ProTx-I inhibits: 1) T-type Ca2+ channel, Cav 3.1 by 84%; 2) Na+ channels, Nav1.2, Nav1.5, Nav1.7, and Nav1.8 by about 80%; and 3) K+ channels, Kv2.1 by 60% and Kv1.3 by 40%. ProTx-I elicits multiple channel blocking activities with certain selectivity, since K+ channel inhibitory activity is relatively weak.
This is one of the first high affinity ligands reported for tetrodotoxin-resistant
Na+
and T-type Ca2+ channels. These ion channels can play a role in
secretion of hormones and neurotransmitters and contribute to cardiovascular
and neuropsychiatric disorders. For example, neuronal T-type Ca2+
channels can contribute to changes in oscillation in the thalamus cells.2
Oscillatory changes have been associated with tremor of Parkinson’s disease,
tinnitus, neuropsychiatric disorders like schizophrenia, and neurogenic
pain. In addition, Ca2+ channels have been implicated as the pace
maker current in the heart and suggested in previous studies to participate
in atrial remodeling.3,4 ProTx-I
peptide should be an extremely useful research tool toward greater
understanding of the role of voltage-gated ion channels in physiology and
disease. |
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1.
R.E. Middleton, V.A. Warren, R.L. Kraus, J.C. Hwang, C.J. Liu, G. Dai, R.M.
Brochu, M.G. Kohler, Y.D. Gao, V.M. Garsky, M.J. Bogusky, J.T. Mehl, C.J.
Cohen, and M.M. Smith, Biochemistry,
41,
14734 (2002). (Original) |
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